Variant 8-132727955-A-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_001382403.1(TMEM71):c.519T>A(p.Asp173Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000107 in 1,613,834 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00024 ( 1 hom., cov: 32)

Exomes 𝑓: 0.000094 ( 0 hom. )

Consequence

TMEM71
NM_001382403.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.435

Variant links:

Genes affected

TMEM71 (HGNC:26572): (transmembrane protein 71) Located in mitochondrion. [provided by Alliance of Genome Resources, Apr 2022]

TMEM71 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=0.01485607).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TMEM71	NM_001382403.1 linkuse as main transcript	c.519T>A	p.Asp173Glu	missense_variant	6/10	ENST00000677595.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TMEM71	ENST00000677595.1 linkuse as main transcript	c.519T>A	p.Asp173Glu	missense_variant	6/10		NM_001382403.1	P1	Q6P5X7-1

Frequencies

GnomAD3 genomes

AF:

0.000237

AC:

AN:

152146

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00183

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:

0.0000882

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000247

AC:

AN:

251008

Hom.:

AF XY:

0.000162

AC XY:

AN XY:

135652

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00156

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:

0.0000529

Gnomad OTH exome

AF:

0.000327

GnomAD4 exome

AF:

0.0000937

AC:

137

AN:

1461570

Hom.:

Cov.:

AF XY:

0.0000811

AC XY:

AN XY:

727076

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00145

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000567

Gnomad4 OTH exome

AF:

0.000149

GnomAD4 genome

AF:

0.000236

AC:

AN:

152264

Hom.:

Cov.:

AF XY:

0.000309

AC XY:

AN XY:

74450

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00183

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000882

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.0000450

Hom.:

Bravo

AF:

0.000295

ExAC

AF:

0.000157

AC:

EpiCase

AF:

0.000109

EpiControl

AF:

0.0000593

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, 2021

The c.462T>A (p.D154E) alteration is located in exon 6 (coding exon 5) of the TMEM71 gene. This alteration results from a T to A substitution at nucleotide position 462, causing the aspartic acid (D) at amino acid position 154 to be replaced by a glutamic acid (E). 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

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.44

Cadd

Benign

Dann

Benign

0.91

Eigen

Benign

-0.61

Eigen_PC

Benign

-0.82

FATHMM_MKL

Benign

0.028

LIST_S2

Benign

0.62

T;T

M_CAP

Benign

0.0039

MetaRNN

Benign

0.015

T;T

MetaSVM

Benign

-0.91

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.29

PROVEAN

Benign

-1.6

N;N

REVEL

Benign

0.14

Sift

Benign

0.12

T;T

Sift4G

Benign

0.084

T;T

Polyphen

0.021

.;B

Vest4

0.22

MutPred

0.28

Gain of catalytic residue at W175 (P = 0.064);.;

MVP

0.19

MPC

0.13

ClinPred

0.054

GERP RS

-4.6

gMVP

0.031

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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