RAMAC

Chr 15

RNA guanine-7 methyltransferase activating subunit

Also known as: C15orf18, FAM103A1, HsT19360, RAM, RAMMET

NCBI Gene: 83640 ENSG00000169612 UniProt: Q9BTL3 OMIM: 614547

RAMAC encodes a regulatory subunit of the mRNA-capping methyltransferase complex that methylates the N7 position of guanosine in the 5'-cap structure of mRNAs and promotes recruitment of the methyl donor S-adenosyl-L-methionine. Mutations cause autosomal recessive intellectual disability with macrocephaly, seizures, and spasticity. The gene shows tolerance to loss-of-function variants with normal constraint metrics.

OMIM ResearchSummary from RefSeq, UniProt

Enables RNA binding activity and enzyme activator activity. Involved in 7-methylguanosine mRNA capping. Located in nucleus. Part of mRNA cap methyltransferase RNMT:RAMAC complex and mRNA capping enzyme complex. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

DNmechanismLOEUF 1.30

Clinical Summary— RAMAC

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Population Constraint (gnomAD)

Low constraint (pLI 0.01) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

23 VUS of 31 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?

1.30LOEUF

pLI 0.008

Z-score 1.04

OE 0.57 (0.28–1.30)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.67Z-score

OE missense 1.24 (1.03–1.49)

79 obs / 63.8 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.57 (0.28–1.30)

0≤0.351.4

Missense OE?1.24 (1.03–1.49)

0≤0.61.4

Synonymous OE?0.64

0≤1.21.6

LoF obs/exp: 4 / 7.0Missense obs/exp: 79 / 63.8Syn Z: 1.33

This gene — mechanism propensity

0.6162th %ile

GOF

0.3293th %ile

LOF

0.4529th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction 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

31 submitted variants in ClinVar

ClinVar

Classification Summary

VUS23

Likely Benign1

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Total
Pathogenic	0	0	0
Likely Pathogenic	0	0	0
VUS	1	22	23
Likely Benign	0	1	1
Benign	0	0	0
Total	1	23	24

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

View in ClinVar →

33 pathogenic / likely-pathogenic (of 37) ClinVar copy-number / structural variants overlap RAMAC — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →