2-97760823-C-A

Position:

• chr2-97760823-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_015348.2(TMEM131):​c.4981G>T​(p.Ala1661Ser) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: TMEM131 NM_015348.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.95

Genes affected

TMEM131 (HGNC:30366): (transmembrane protein 131) Predicted to be integral component of membrane. Predicted to be active in membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.41704977).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM131	NM_015348.2	c.4981G>T	p.Ala1661Ser	missense_variant	37/41	ENST00000186436.10	NP_056163.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMEM131	ENST00000186436.10	c.4981G>T	p.Ala1661Ser	missense_variant	37/41	5	NM_015348.2	ENSP00000186436	P1
TMEM131	ENST00000485245.2	n.4495G>T		non_coding_transcript_exon_variant	1/2	1
TMEM131	ENST00000465767.1	n.375G>T		non_coding_transcript_exon_variant	1/3	3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

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 24, 2023

The c.4981G>T (p.A1661S) alteration is located in exon 37 (coding exon 37) of the TMEM131 gene. This alteration results from a G to T substitution at nucleotide position 4981, causing the alanine (A) at amino acid position 1661 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	Benign	0.31
BayesDel_addAF	Benign	-0.034	T
BayesDel_noAF	Benign	-0.29
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.082	T
Eigen	Uncertain	0.26
Eigen_PC	Uncertain	0.31
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.42	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	1.0	L
MutationTaster	Benign	1.0	D
PrimateAI	Uncertain	0.65	T
PROVEAN	Benign	-0.38	N
REVEL	Benign	0.11
Sift	Pathogenic	0.0	D
Sift4G	Benign	0.39	T
Polyphen		0.75	P
Vest4		0.64
MutPred		0.23		Gain of glycosylation at A1661 (P = 0.0679);
MVP		0.082
MPC		0.72
ClinPred		0.81	D
GERP RS		4.6
Varity_R		0.38
gMVP		0.46

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr2-98377286;