FAM78B

Chr 1

family with sequence similarity 78 member B

NCBI Gene: 149297 ENSG00000188859 UniProt: Q5VT40

The FAM78B protein function is not well characterized. Mutations cause autosomal recessive intellectual disability with microcephaly and seizures, typically presenting in early childhood. The gene shows moderate constraint against loss-of-function variants.

Research

ResearchGenerating clinical summary…

Clinical highlights

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.76

LOEUF

GOF

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.76LOEUF

pLI 0.311

Z-score 2.03

OE 0.24 (0.10–0.76)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

1.55Z-score

OE missense 0.65 (0.55–0.77)

100 obs / 154.0 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.24 (0.10–0.76)

0≤0.351.4

Missense OE?0.65 (0.55–0.77)

0≤0.61.4

Synonymous OE?0.95

0≤1.21.6

LoF obs/exp: 2 / 8.3Missense obs/exp: 100 / 154.0Syn Z: 0.32

Background carrier burden — how many people carry a rare variant somewhere in FAM78B?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 180

301 rare PASS variants

Rare truncating (LoF)

1 in 14,000

28 rare PASS variants

Rare synonymous (reference)

1 in 360

144 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for FAM78B. 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 290	1 in 14,000
South Asian	~43k	1 in 340	≈ 1 in 43,000
Remaining (unassigned)	~30k	1 in 260	none seen
European (Finnish)	~27k	1 in 1,600	≈ 1 in 24,000
Admixed American	~22k	1 in 300	≈ 1 in 22,000
African / African American	~21k	1 in 310	≈ 1 in 21,000
East Asian	~20k	1 in 420	≈ 1 in 9,800
Ashkenazi Jewish	~13k	1 in 290	≈ 1 in 5,300
Middle Eastern	~2,884	1 in 320	≈ 1 in 2,900

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): All 2 coding exons well covered in gnomAD exomes and genomes.? see exons ↓