Variant 6-158573511-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The ENST00000367090.4(TMEM181):c.223G>A(p.Val75Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000213 in 1,453,108 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V75F) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.000021 ( 0 hom. )

Consequence

TMEM181
ENST00000367090.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.79

Variant links:

Genes affected

TMEM181 (HGNC:20958): (transmembrane protein 181) The TMEM181 gene encodes a putative G protein-coupled receptor expressed on the cell surface (Carette et al., 2009 [PubMed 19965467]; Wollscheid et al., 2009 [PubMed 19349973]).[supplied by OMIM, Jan 2010]

TMEM181 links:

TMEM181 (HGNC:):

TMEM181 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.034552127).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM181	NM_001376852.1 linkuse as main transcript	c.100G>A	p.Val34Ile	missense_variant	2/17	ENST00000684151.1	NP_001363781.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMEM181	ENST00000684151.1 linkuse as main transcript	c.100G>A	p.Val34Ile	missense_variant	2/17		NM_001376852.1	ENSP00000507085.1		A0A804HII6
TMEM181	ENST00000367090.4 linkuse as main transcript	c.223G>A	p.Val75Ile	missense_variant	2/17	1		ENSP00000356057.4		Q9P2C4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000432

AC:

AN:

231320

Hom.:

AF XY:

0.00000799

AC XY:

AN XY:

125204

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000599

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000213

AC:

AN:

1453108

Hom.:

Cov.:

AF XY:

0.0000222

AC XY:

AN XY:

721978

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000738

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000181

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000227

ExAC

AF:

0.00000827

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 20, 2023

The c.511G>A (p.V171I) alteration is located in exon 2 (coding exon 2) of the TMEM181 gene. This alteration results from a G to A substitution at nucleotide position 511, causing the valine (V) at amino acid position 171 to be replaced by an isoleucine (I). 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

0.077

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.58

CADD

Benign

DANN

Benign

0.65

DEOGEN2

Benign

0.0057

Eigen

Benign

-0.67

Eigen_PC

Benign

-0.44

FATHMM_MKL

Benign

0.60

LIST_S2

Benign

0.85

M_CAP

Benign

0.0016

MetaRNN

Benign

0.035

MetaSVM

Benign

-0.94

MutationAssessor

Benign

-0.81

MutationTaster

Benign

0.67

PrimateAI

Benign

0.35

PROVEAN

Benign

0.21

REVEL

Benign

0.060

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0060

Vest4

0.087

MutPred

0.23

Loss of sheet (P = 0.0457);

MVP

0.055

MPC

0.14

ClinPred

0.17

GERP RS

1.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.024

gMVP

0.11

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over