rs17854363

Positions:

• chr7-143356630-C-A
• chr7-143356630-C-G
• chr7-143356630-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001031690.3(FAM131B):​c.1003G>T​(p.Ala335Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 31)
• Consequence: FAM131B NM_001031690.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.98

Genes affected

FAM131B (HGNC:22202): (family with sequence similarity 131 member B) Located in cytosol and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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=0.12577939).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FAM131B	NM_001031690.3	c.1003G>T	p.Ala335Ser	missense_variant	7/7	ENST00000443739.7	NP_001026860.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FAM131B	ENST00000443739.7	c.1003G>T	p.Ala335Ser	missense_variant	7/7	1	NM_001031690.3	ENSP00000410603	P1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.077
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	21
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0047	.;.;T;T;T
Eigen	Benign	0.034
Eigen_PC	Benign	0.20
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Benign	0.70	T;T;.;.;T
M_CAP	Benign	0.0052	T
MetaRNN	Benign	0.13	T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.0	.;.;L;L;L
MutationTaster	Benign	0.96	D;D;D;D;D
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	-0.19	N;N;N;N;N
REVEL	Benign	0.090
Sift	Benign	0.59	T;T;T;T;T
Sift4G	Benign	0.71	T;T;T;T;T
Polyphen		0.18, 0.45	.;B;B;B;B
Vest4		0.28
MutPred		0.075		.;.;Gain of phosphorylation at A307 (P = 0.0042);Gain of phosphorylation at A307 (P = 0.0042);Gain of phosphorylation at A307 (P = 0.0042);
MVP		0.12
MPC		0.38
ClinPred		0.23	T
GERP RS		5.8
Varity_R		0.058
gMVP		0.036

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs17854363; hg19: chr7-143053723;