Variant 8-73975891-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The ENST00000520167.5(TMEM70):n.247T>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0161 in 164,072 control chromosomes in the GnomAD database, including 49 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.017 ( 49 hom., cov: 33)

Exomes 𝑓: 0.0013 ( 0 hom. )

Consequence

TMEM70
ENST00000520167.5 non_coding_transcript_exon

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.108

Variant links:

Genes affected

TMEM70 (HGNC:26050): (transmembrane protein 70) This gene likely encodes a mitochondrial membrane protein. The encoded protein may play a role in biogenesis of mitochondrial ATP synthase. Mutations in this gene have been associated with neonatal mitochondrial encephalocardiomyopathy due to ATP synthase deficiency. Alternatively spliced transcript variants have been described. [provided by RefSeq, Feb 2010]

TMEM70 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.76).

BP6

Variant 8-73975891-T-A is Benign according to our data. Variant chr8-73975891-T-A is described in ClinVar as [Likely_benign]. Clinvar id is 1212724.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0173 (2632/152106) while in subpopulation NFE AF= 0.025 (1699/67972). AF 95% confidence interval is 0.024. There are 49 homozygotes in gnomad4. There are 1254 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 49 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMEM70	ENST00000520167.5 linkuse as main transcript	n.247T>A		non_coding_transcript_exon_variant	2/4	2
TMEM70	ENST00000523794.1 linkuse as main transcript	n.504T>A		non_coding_transcript_exon_variant	2/3	3

Frequencies

GnomAD3 genomes

AF:

0.0173

AC:

2632

AN:

151988

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00413

Gnomad AMI

AF:

0.0340

Gnomad AMR

AF:

0.0179

Gnomad ASJ

AF:

0.0556

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00664

Gnomad FIN

AF:

0.0157

Gnomad MID

AF:

0.0605

Gnomad NFE

AF:

0.0250

Gnomad OTH

AF:

0.0225

GnomAD4 exome

AF:

0.00134

AC:

AN:

11966

Hom.:

Cov.:

AF XY:

0.00143

AC XY:

AN XY:

6284

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00127

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00424

Gnomad4 NFE exome

AF:

0.00160

Gnomad4 OTH exome

AF:

0.00362

GnomAD4 genome

AF:

0.0173

AC:

2632

AN:

152106

Hom.:

Cov.:

AF XY:

0.0169

AC XY:

1254

AN XY:

74352

show subpopulations

Gnomad4 AFR

AF:

0.00414

Gnomad4 AMR

AF:

0.0177

Gnomad4 ASJ

AF:

0.0556

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00664

Gnomad4 FIN

AF:

0.0157

Gnomad4 NFE

AF:

0.0250

Gnomad4 OTH

AF:

0.0228

Alfa

AF:

0.0266

Hom.:

Bravo

AF:

0.0171

Asia WGS

AF:

0.00404

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 07, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.76

CADD

Benign

7.0

DANN

Benign

0.83

Splicing

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