Genetic Variant FAM76B:p.Ala311Thr (chr11-95771650-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_144664.5(FAM76B):c.931G>A(p.Ala311Thr) variant causes a missense, splice region change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

FAM76B
NM_144664.5 missense, splice_region

Scores

Splicing: ADA: 0.8063

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.13

Variant links:

Genes affected

FAM76B (HGNC:28492): (family with sequence similarity 76 member B) Located in nuclear speck. [provided by Alliance of Genome Resources, Apr 2022]

FAM76B links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.13519135).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM76B	NM_144664.5 link	c.931G>A	p.Ala311Thr	missense_variant, splice_region_variant	Exon 10 of 10	ENST00000358780.10	NP_653265.3	Q5HYJ3-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAM76B	ENST00000358780.10 link	c.931G>A	p.Ala311Thr	missense_variant, splice_region_variant	Exon 10 of 10	1	NM_144664.5	ENSP00000351631.5		Q5HYJ3-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1451296

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

721892

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Feb 25, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.931G>A (p.A311T) alteration is located in exon 10 (coding exon 10) of the FAM76B gene. This alteration results from a G to A substitution at nucleotide position 931, causing the alanine (A) at amino acid position 311 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.078

BayesDel_addAF

Benign

-0.054

BayesDel_noAF

Benign

-0.32

CADD

Uncertain

DANN

Benign

0.96

DEOGEN2

Benign

0.025

T;T

Eigen

Benign

-0.12

Eigen_PC

Benign

0.095

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.92

D;D

M_CAP

Benign

0.0050

MetaRNN

Benign

0.14

T;T

MetaSVM

Benign

-0.94

MutationAssessor

Benign

0.44

N;.

PrimateAI

Pathogenic

0.81

PROVEAN

Benign

-0.15

N;N

REVEL

Benign

0.079

Sift

Benign

0.61

T;T

Sift4G

Benign

0.57

T;T

Polyphen

0.026

B;.

Vest4

0.32

MutPred

0.13

Gain of phosphorylation at A311 (P = 0.0698);.;

MVP

0.41

MPC

0.26

ClinPred

0.75

GERP RS

5.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.13

gMVP

0.053

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.81

dbscSNV1_RF

Benign

0.63

SpliceAI score (max)

0.11

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over