Variant 9-136791958-G-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The ENST00000290079.9(TMEM141):c.133G>T(p.Ala45Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000401 in 1,614,014 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00042 ( 0 hom. )

Consequence

TMEM141
ENST00000290079.9 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.659

Variant links:

Genes affected

TMEM141 (HGNC:28211): (transmembrane protein 141) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

TMEM141 links:

ENSG00000272896 (HGNC:):

ENSG00000272896 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM141	NM_032928.4 linkuse as main transcript	c.133G>T	p.Ala45Ser	missense_variant	3/5	ENST00000290079.9	NP_116317.1	Q96I45

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMEM141	ENST00000290079.9 linkuse as main transcript	c.133G>T	p.Ala45Ser	missense_variant	3/5	1	NM_032928.4	ENSP00000290079.8		Q96I45
ENSG00000272896	ENST00000456614.2 linkuse as main transcript	n.57G>T		non_coding_transcript_exon_variant	2/6	4		ENSP00000476927.2		V9GYN2

Frequencies

GnomAD3 genomes

AF:

0.000197

AC:

AN:

152238

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000397

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000171

AC:

AN:

251364

Hom.:

AF XY:

0.000199

AC XY:

AN XY:

135886

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000352

Gnomad OTH exome

AF:

0.000326

GnomAD4 exome

AF:

0.000423

AC:

618

AN:

1461776

Hom.:

Cov.:

AF XY:

0.000437

AC XY:

318

AN XY:

727176

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000537

Gnomad4 OTH exome

AF:

0.000199

GnomAD4 genome

AF:

0.000197

AC:

AN:

152238

Hom.:

Cov.:

AF XY:

0.000255

AC XY:

AN XY:

74380

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000397

Gnomad4 OTH

AF:

0.000478

Alfa

AF:

0.000427

Hom.:

Bravo

AF:

0.000223

TwinsUK

AF:

0.00108

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.000132

AC:

EpiCase

AF:

0.000709

EpiControl

AF:

0.000533

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

Mar 23, 2022

The c.133G>T (p.A45S) alteration is located in exon 3 (coding exon 3) of the TMEM141 gene. This alteration results from a G to T substitution at nucleotide position 133, causing the alanine (A) at amino acid position 45 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

0.11

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.48

CADD

Benign

DANN

Benign

0.91

DEOGEN2

Benign

0.028

Eigen

Benign

-0.84

Eigen_PC

Benign

-0.94

FATHMM_MKL

Benign

0.067

LIST_S2

Benign

0.59

M_CAP

Benign

0.023

MetaRNN

Benign

0.057

MetaSVM

Benign

-0.98

MutationTaster

Benign

1.0

PrimateAI

Benign

0.28

PROVEAN

Benign

-1.3

REVEL

Benign

0.041

Sift

Benign

0.32

Sift4G

Benign

0.11

Polyphen

0.14

Vest4

0.34

MVP

0.014

MPC

0.28

ClinPred

0.046

GERP RS

-0.38

RBP_binding_hub_radar

0.92

RBP_regulation_power_radar

2.6

Varity_R

0.050

gMVP

0.41

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.23

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.23

Position offset: 15

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