8-73976049-A-AGGCGGCAGGCGGGCGGCAGGCGGGCGGCAGGCG

Position:

• chr8-73976049-A-AGGCGGCAGGCGGGCGGCAGGCGGGCGGCAGGCG

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The ENST00000520167.5(TMEM70):​n.317+141_317+173dup variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: 𝑓 0.026 (340 hom., cov: 0)
• Consequence: TMEM70 ENST00000520167.5 intron, non_coding_transcript
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.111

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 -10 ACMG points.

• BP6: Variant 8-73976049-A-AGGCGGCAGGCGGGCGGCAGGCGGGCGGCAGGCG is Benign according to our data. Variant chr8-73976049-A-AGGCGGCAGGCGGGCGGCAGGCGGGCGGCAGGCG is described in ClinVar as [Likely_benign]. Clinvar id is 1707282.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.0263 (2726/103474) while in subpopulation EAS AF= 0.0428 (129/3014). AF 95% confidence interval is 0.0368. There are 340 homozygotes in gnomad4. There are 1260 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 340 AR gene

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+141_317+173dup		intron_variant, non_coding_transcript_variant		2
TMEM70	ENST00000523794.1	n.574+141_575-171dup		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.0263 AC: 2723 AN: 103386 Hom.: 341 Cov.: 0

Gnomad AFR AF: 0.0185

Gnomad AMI AF: 0.0707

Gnomad AMR AF: 0.0257

Gnomad ASJ AF: 0.0141

Gnomad EAS AF: 0.0425

Gnomad SAS AF: 0.0195

Gnomad FIN AF: 0.0279

Gnomad MID AF: 0.00413

Gnomad NFE AF: 0.0319

Gnomad OTH AF: 0.0183

GnomAD4 exome Cov.: 0

GnomAD4 genome AF: 0.0263 AC: 2726 AN: 103474 Hom.: 340 Cov.: 0 AF XY: 0.0251 AC XY: 1260 AN XY: 50248

Gnomad4 AFR AF: 0.0185

Gnomad4 AMR AF: 0.0257

Gnomad4 ASJ AF: 0.0141

Gnomad4 EAS AF: 0.0428

Gnomad4 SAS AF: 0.0186

Gnomad4 FIN AF: 0.0279

Gnomad4 NFE AF: 0.0320

Gnomad4 OTH AF: 0.0189

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

May 26, 2021

See Variant Classification Assertion Criteria. -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs71269968; hg19: chr8-74888284;