2-97757310-C-T

Variant names:

• chr2-97757310-C-T
• rs530863994
• NM_015348.2:c.5441G>A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_015348.2(TMEM131):​c.5441G>A​(p.Ser1814Asn) 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. 15/24 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S1814T) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: TMEM131 NM_015348.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.05
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015348.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM131	NM_015348.2	MANE Select	c.5441G>A	p.Ser1814Asn	missense	Exon 41 of 41	NP_056163.1	Q92545

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM131	ENST00000186436.10	TSL:5 MANE Select	c.5441G>A	p.Ser1814Asn	missense	Exon 41 of 41	ENSP00000186436.5	Q92545
	TMEM131	ENST00000485245.2	TSL:1	n.6499G>A		non_coding_transcript_exon	Exon 2 of 2
	TMEM131	ENST00000962018.1		c.5492G>A	p.Ser1831Asn	missense	Exon 42 of 42	ENSP00000632077.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000312 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.055
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.78
CADD	Benign	14
DANN	Benign	0.30
DEOGEN2	Benign	0.0084	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.28	N
LIST_S2	Benign	0.67	T
M_CAP	Benign	0.0020	T
MetaRNN	Benign	0.028	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	-0.55	N
PhyloP100		1.0
PrimateAI	Benign	0.28	T
PROVEAN	Benign	1.0	N
REVEL	Benign	0.054
Sift	Benign	1.0	T
Sift4G	Benign	0.67	T
Polyphen		0.0	B
Vest4		0.047
MutPred		0.13		Loss of phosphorylation at S1810 (P = 0.1103)
MVP		0.043
MPC		0.18
ClinPred		0.052	T
GERP RS		-2.4
Varity_R		0.024
gMVP		0.078
Mutation Taster		=94/6	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.39		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.39		Position offset: -27

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

Other links and lift over

dbSNP: rs530863994; hg19: chr2-98373773;