GCSAML

Chr 1

germinal center associated signaling and motility like

Also known as: C1orf150

This gene encodes a signaling molecule associated with germinal centers where mature B lymphocytes proliferate and differentiate. The gene shows low constraint to loss-of-function variation (pLI 0.12, LOEUF 1.15), and no definitive disease associations have been established in the provided data.

ResearchSummary from RefSeq

This gene encodes a protein thought to be a signaling molecule associated with germinal centers, the sites of proliferation and differentiation of mature B lymphocytes. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Aug 2013]

ResearchGenerating clinical summary…

MultiplemechanismLOEUF 1.15

Clinical Summary— GCSAML

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Population Constraint (gnomAD)

Low constraint (pLI 0.12) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

58 VUS of 64 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.15LOEUF

pLI 0.125

Z-score 1.37

OE 0.37 (0.15–1.15)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.31Z-score

OE missense 1.11 (0.92–1.35)

73 obs / 65.9 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.37 (0.15–1.15)

0≤0.351.4

Missense OE?1.11 (0.92–1.35)

0≤0.61.4

Synonymous OE?0.63

0≤1.21.6

LoF obs/exp: 2 / 5.4Missense obs/exp: 73 / 65.9Syn Z: 1.43

This gene — mechanism propensity

0.82top 10%

GOF

0.81top 10%

LOF

0.1895th %ile

This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

DNprediction above median

GOFprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

64 submitted variants in ClinVar

ClinVar

Classification Summary

VUS58

VUS

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Total
Pathogenic	0	0
Likely Pathogenic	0	0
VUS	58	58
Likely Benign	0	0
Benign	0	0
Total	58	58

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

70 pathogenic / likely-pathogenic (of 93) ClinVar copy-number / structural variants overlap GCSAML — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →