8-73976018-C-A

Position:

• chr8-73976018-C-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000520167.5(TMEM70):​n.317+57C>A variant causes a intron, non coding transcript 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, non_coding_transcript
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.853

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]

ACMG classification

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	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TMEM70	ENST00000520167.5	n.317+57C>A		intron_variant, non_coding_transcript_variant		2
TMEM70	ENST00000523794.1	n.574+57C>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.0179 AC: 2625 AN: 146940 Hom.: 38 Cov.: 33

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.: 0 AF XY: 0.149 AC XY: 7684 AN XY: 51540

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.: 40 Cov.: 33 AF XY: 0.0196 AC XY: 1405 AN XY: 71812

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.: 1

Bravo AF: 0.0144

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

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	Jun 14, 2018	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

Other links and lift over

dbSNP: rs141235801; hg19: chr8-74888253;