ST20-MTHFS

Chr 15

ST20-MTHFS readthrough

This locus represents naturally occurring read-through transcription between the neighboring suppressor of tumorigenicity 20 and 5,10-methenyltetrahydrofolate synthetase (5-formyltetrahydrofolate cyclo-ligase) genes on chromosome 15. The read-through transcript produces a fusion protein that shares sequence identity with each individual gene product. [provided by RefSeq, Dec 2010]

Research

ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.34

LOEUF

—

Mechanism

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.34LOEUF

pLI 0.008

Z-score 0.99

OE 0.59 (0.29–1.34)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.56Z-score

OE missense 0.84 (0.70–1.01)

83 obs / 98.6 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.59 (0.29–1.34)

0≤0.351.4

Missense OE?0.84 (0.70–1.01)

0≤0.61.4

Synonymous OE?1.00

0≤1.21.6

LoF obs/exp: 4 / 6.8Missense obs/exp: 83 / 98.6Syn Z: 0.02

Background carrier burden — how many people carry a rare variant somewhere in ST20-MTHFS?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 210

231 rare PASS variants

Rare truncating (LoF)

1 in 1,300

36 rare PASS variants

Rare synonymous (reference)

1 in 700

90 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for ST20-MTHFS. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 250	1 in 1,200
South Asian	~43k	1 in 320	1 in 1,900
Remaining (unassigned)	~30k	1 in 170	1 in 1,500
European (Finnish)	~27k	1 in 390	none seen
Admixed American	~22k	1 in 160	1 in 740
African / African American	~21k	1 in 220	1 in 2,300
East Asian	~20k	1 in 130	1 in 660
Ashkenazi Jewish	~13k	1 in 2,100	≈ 1 in 4,000
Middle Eastern	~2,884	1 in 180	≈ 1 in 920

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 2 of 3 coding exons well covered in gnomAD exomes; exon 2 poorly covered. Genomes: all 3.? see exons ↓