7-143356581-A-G

Position:

• chr7-143356581-A-G

Variant summary

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

The NM_001031690.3(FAM131B):​c.1052T>C​(p.Phe351Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 30)
• Consequence: FAM131B NM_001031690.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.25

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FAM131B	NM_001031690.3	c.1052T>C	p.Phe351Ser	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.1052T>C	p.Phe351Ser	missense_variant	7/7	1	NM_001031690.3	ENSP00000410603.2

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 30

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 29, 2024

The c.1052T>C (p.F351S) alteration is located in exon 7 (coding exon 7) of the FAM131B gene. This alteration results from a T to C substitution at nucleotide position 1052, causing the phenylalanine (F) at amino acid position 351 to be replaced by a serine (S). 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	Pathogenic	0.98
BayesDel_addAF	Pathogenic	0.20	D
BayesDel_noAF	Uncertain	0.040
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.019	.;.;T;T;T
Eigen	Uncertain	0.64
Eigen_PC	Uncertain	0.64
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.80	T;T;.;.;T
M_CAP	Benign	0.029	D
MetaRNN	Uncertain	0.46	T;T;T;T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	1.5	.;.;L;L;L
PrimateAI	Uncertain	0.79	T
PROVEAN	Benign	-1.6	N;N;N;N;N
REVEL	Benign	0.25
Sift	Uncertain	0.0030	D;D;D;D;D
Sift4G	Uncertain	0.035	D;D;D;D;D
Polyphen		1.0	.;D;D;D;D
Vest4		0.59
MutPred		0.18		.;.;Gain of phosphorylation at F323 (P = 0.0084);Gain of phosphorylation at F323 (P = 0.0084);Gain of phosphorylation at F323 (P = 0.0084);
MVP		0.29
MPC		1.6
ClinPred		0.85	D
GERP RS		5.8
Varity_R		0.25
gMVP		0.32

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-143053674; COSMIC: COSV100577652; COSMIC: COSV100577652;