chr8-132727818-T-C

Position:

• chr8-132727818-T-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001382403.1(TMEM71):​c.656A>G​(p.Glu219Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000137 in 1,459,732 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/17 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000014 (0 hom.)
• Consequence: TMEM71 NM_001382403.1 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0490

Genes affected

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

ACMG classification

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=0.054968804).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM71	NM_001382403.1	c.656A>G	p.Glu219Gly	missense_variant	6/10	ENST00000677595.1	NP_001369332.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMEM71	ENST00000677595.1	c.656A>G	p.Glu219Gly	missense_variant	6/10		NM_001382403.1	ENSP00000504388.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.0000201 AC: 5 AN: 248872 Hom.: 0 AF XY: 0.0000297 AC XY: 4 AN XY: 134516

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000117

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: 0.00000889

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000137 AC: 20 AN: 1459732 Hom.: 0 Cov.: 31 AF XY: 0.0000138 AC XY: 10 AN XY: 726168

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000902

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: 0.0000135

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ExAC AF: 0.00000824 AC: 1

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 12, 2024

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.39	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	6.4
DANN	Uncertain	0.99
Eigen	Benign	-0.87
Eigen_PC	Benign	-0.96
FATHMM_MKL	Benign	0.015	N
LIST_S2	Benign	0.56	T;T
M_CAP	Benign	0.0014	T
MetaRNN	Benign	0.055	T;T
MetaSVM	Benign	-1.0	T
PrimateAI	Benign	0.21	T
PROVEAN	Benign	-2.2	N;N
REVEL	Benign	0.020
Sift	Benign	0.17	T;T
Sift4G	Benign	0.26	T;T
Polyphen		0.0040	.;B
Vest4		0.063
MutPred		0.16		Loss of helix (P = 0.0093);.;
MVP		0.18
MPC		0.047
ClinPred		0.035	T
GERP RS		-0.36
gMVP		0.090

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

Other links and lift over

dbSNP: rs756497845; hg19: chr8-133740064;