7-143356815-G-C

Position:

• chr7-143356815-G-C

Variant summary

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

The NM_001031690.3(FAM131B):​c.818C>G​(p.Ser273Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: FAM131B NM_001031690.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.09

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=0.10349241).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FAM131B	NM_001031690.3	c.818C>G	p.Ser273Cys	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.818C>G	p.Ser273Cys	missense_variant	7/7	1	NM_001031690.3	ENSP00000410603.2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 31

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

Dec 03, 2021

The c.818C>G (p.S273C) alteration is located in exon 7 (coding exon 7) of the FAM131B gene. This alteration results from a C to G substitution at nucleotide position 818, causing the serine (S) at amino acid position 273 to be replaced by a cysteine (C). 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	0.073
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0095	.;.;T;T;T
Eigen	Benign	-0.13
Eigen_PC	Benign	-0.060
FATHMM_MKL	Benign	0.14	N
LIST_S2	Benign	0.80	T;T;.;.;T
M_CAP	Benign	0.0075	T
MetaRNN	Benign	0.10	T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.7	.;.;L;L;L
PrimateAI	Benign	0.48	T
PROVEAN	Benign	-0.25	N;N;N;N;N
REVEL	Benign	0.057
Sift	Benign	0.053	T;T;T;T;T
Sift4G	Benign	0.10	T;T;T;T;T
Polyphen		0.0010, 0.93	.;B;P;P;P
Vest4		0.12
MutPred		0.35		.;.;Gain of catalytic residue at S245 (P = 0.0065);Gain of catalytic residue at S245 (P = 0.0065);Gain of catalytic residue at S245 (P = 0.0065);
MVP		0.043
MPC		0.83
ClinPred		0.24	T
GERP RS		4.6
Varity_R		0.046
gMVP		0.14

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: chr7-143053908;