Variant 10-80090895-G-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_025125.4(TMEM254):c.350G>T(p.Arg117Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000561 in 1,613,734 control chromosomes in the GnomAD database, including 1 homozygotes. 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 (★).

Frequency

Genomes: 𝑓 0.00052 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00057 ( 1 hom. )

Consequence

TMEM254
NM_025125.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.03

Variant links:

Genes affected

TMEM254 (HGNC:25804): (transmembrane protein 254) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

TMEM254 links:

TMEM254 (HGNC:):

TMEM254 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=0.008805484).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM254	NM_025125.4 linkuse as main transcript	c.350G>T	p.Arg117Leu	missense_variant	4/4	ENST00000372281.8	NP_079401.2	Q8TBM7-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMEM254	ENST00000372281.8 linkuse as main transcript	c.350G>T	p.Arg117Leu	missense_variant	4/4	1	NM_025125.4	ENSP00000361355.3		Q8TBM7-1

Frequencies

GnomAD3 genomes

AF:

0.000519

AC:

AN:

152084

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000145

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000458

Gnomad ASJ

AF:

0.000578

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000897

Gnomad OTH

AF:

0.00144

GnomAD3 exomes

AF:

0.000523

AC:

131

AN:

250586

Hom.:

AF XY:

0.000480

AC XY:

AN XY:

135430

show subpopulations

Gnomad AFR exome

AF:

0.000494

Gnomad AMR exome

AF:

0.000349

Gnomad ASJ exome

AF:

0.00149

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000329

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000749

Gnomad OTH exome

AF:

0.00163

GnomAD4 exome

AF:

0.000565

AC:

826

AN:

1461532

Hom.:

Cov.:

AF XY:

0.000575

AC XY:

418

AN XY:

727050

show subpopulations

Gnomad4 AFR exome

AF:

0.000359

Gnomad4 AMR exome

AF:

0.000336

Gnomad4 ASJ exome

AF:

0.000765

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000464

Gnomad4 FIN exome

AF:

0.0000562

Gnomad4 NFE exome

AF:

0.000655

Gnomad4 OTH exome

AF:

0.000580

GnomAD4 genome

AF:

0.000519

AC:

AN:

152202

Hom.:

Cov.:

AF XY:

0.000484

AC XY:

AN XY:

74402

show subpopulations

Gnomad4 AFR

AF:

0.000144

Gnomad4 AMR

AF:

0.000458

Gnomad4 ASJ

AF:

0.000578

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000897

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.000873

Hom.:

Bravo

AF:

0.000578

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.00104

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.000581

AC:

ExAC

AF:

0.000568

AC:

EpiCase

AF:

0.00131

EpiControl

AF:

0.00136

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

Oct 18, 2021

The c.350G>T (p.R117L) alteration is located in exon 4 (coding exon 4) of the TMEM254 gene. This alteration results from a G to T substitution at nucleotide position 350, causing the arginine (R) at amino acid position 117 to be replaced by a leucine (L). 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

0.14

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.40

CADD

Benign

DANN

Benign

0.94

DEOGEN2

Benign

0.13

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.015

LIST_S2

Benign

0.62

M_CAP

Benign

0.0038

MetaRNN

Benign

0.0088

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.55

PrimateAI

Benign

0.31

PROVEAN

Benign

-1.5

REVEL

Benign

0.053

Sift

Uncertain

0.0070

Sift4G

Uncertain

0.030

Polyphen

0.10

Vest4

0.14

MVP

0.076

MPC

0.060

ClinPred

0.013

GERP RS

2.2

Varity_R

0.094

gMVP

0.30

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