chr2-97760620-G-A

Position:

• chr2-97760620-G-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_015348.2(TMEM131):​c.5081C>T​(p.Ala1694Val) 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. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: TMEM131 NM_015348.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.12

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]

TMEM131 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.052203506).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM131	NM_015348.2	c.5081C>T	p.Ala1694Val	missense_variant	38/41	ENST00000186436.10	NP_056163.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMEM131	ENST00000186436.10	c.5081C>T	p.Ala1694Val	missense_variant	38/41	5	NM_015348.2	ENSP00000186436.5
TMEM131	ENST00000485245.2	n.4698C>T		non_coding_transcript_exon_variant	1/2	1
TMEM131	ENST00000465767.1	n.475C>T		non_coding_transcript_exon_variant	2/3	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

Jun 23, 2021

The c.5081C>T (p.A1694V) alteration is located in exon 38 (coding exon 38) of the TMEM131 gene. This alteration results from a C to T substitution at nucleotide position 5081, causing the alanine (A) at amino acid position 1694 to be replaced by a valine (V). 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	0.069
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	19
DANN	Benign	0.87
DEOGEN2	Benign	0.010	T
Eigen	Benign	-0.47
Eigen_PC	Benign	-0.28
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Benign	0.79	T
M_CAP	Benign	0.0049	T
MetaRNN	Benign	0.052	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.34	N
PrimateAI	Benign	0.22	T
PROVEAN	Benign	0.21	N
REVEL	Benign	0.037
Sift	Benign	0.49	T
Sift4G	Benign	0.089	T
Polyphen		0.0	B
Vest4		0.14
MutPred		0.12		Gain of sheet (P = 0.039);
MVP		0.043
MPC		0.19
ClinPred		0.16	T
GERP RS		3.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.017
gMVP		0.15

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: rs1678784148; hg19: chr2-98377083;