Genetic Variant ENST00000520167.5:n.317+57C>A (chr8-73976018-C-A) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000520167.5(TMEM70):n.317+57C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0681 in 241,456 control chromosomes in the GnomAD database, including 6,168 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.018 ( 40 hom., cov: 33)

Exomes 𝑓: 0.15 ( 6128 hom. )

Consequence

TMEM70
ENST00000520167.5 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.853

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=-0.82).

BP6

Variant 8-73976018-C-A is Benign according to our data. Variant chr8-73976018-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 676048.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAdExome4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.174 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein	UniProt
TMEM70	NM_017866.6 link	c.-264C>A	upstream_gene_variant	ENST00000312184.6	NP_060336.3	Q9BUB7-1
TMEM70	NM_001040613.3 link	c.-264C>A	upstream_gene_variant		NP_001035703.1	Q9BUB7-3
TMEM70	NR_033334.2 link	n.-177C>A	upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMEM70	ENST00000312184.6 link	c.-264C>A		upstream_gene_variant		1	NM_017866.6	ENSP00000312599.5		Q9BUB7-1

Frequencies

GnomAD3 genomes

AF:

0.0179

AC:

2625

AN:

146940

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00653

Gnomad AMI

AF:

0.00341

Gnomad AMR

AF:

0.0132

Gnomad ASJ

AF:

0.0228

Gnomad EAS

AF:

0.0158

Gnomad SAS

AF:

0.0357

Gnomad FIN

AF:

0.0505

Gnomad MID

AF:

0.0226

Gnomad NFE

AF:

0.0198

Gnomad OTH

AF:

0.0181

GnomAD4 exome

AF:

0.146

AC:

13813

AN:

94410

Hom.:

6128

Cov.:

AF XY:

0.149

AC XY:

7684

AN XY:

51540

show subpopulations

Gnomad4 AFR exome

AF:

0.0290

Gnomad4 AMR exome

AF:

0.0503

Gnomad4 ASJ exome

AF:

0.0956

Gnomad4 EAS exome

AF:

0.147

Gnomad4 SAS exome

AF:

0.180

Gnomad4 FIN exome

AF:

0.341

Gnomad4 NFE exome

AF:

0.145

Gnomad4 OTH exome

AF:

0.128

GnomAD4 genome

AF:

0.0179

AC:

2634

AN:

147046

Hom.:

Cov.:

AF XY:

0.0196

AC XY:

1405

AN XY:

71812

show subpopulations

Gnomad4 AFR

AF:

0.00669

Gnomad4 AMR

AF:

0.0131

Gnomad4 ASJ

AF:

0.0228

Gnomad4 EAS

AF:

0.0158

Gnomad4 SAS

AF:

0.0357

Gnomad4 FIN

AF:

0.0505

Gnomad4 NFE

AF:

0.0198

Gnomad4 OTH

AF:

0.0189

Alfa

AF:

0.00880

Hom.:

Bravo

AF:

0.0144

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 14, 2018

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

2.3

DANN

Benign

0.64

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