chr8-73976049-AGGCGGCAGGCGGGCGGCAGGCG-A

Position:

• chr8-73976049-AGGCGGCAGGCGGGCGGCAGGCG-A

Variant summary

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

The ENST00000520167.5(TMEM70):​n.317+152_317+173del 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 0.012 in 226,034 control chromosomes in the GnomAD database, including 73 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.016 (22 hom., cov: 0)
  • Exomes 𝑓: 0.0084 (51 hom.)
• Consequence: TMEM70 ENST00000520167.5 intron, non_coding_transcript
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.351

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-AGGCGGCAGGCGGGCGGCAGGCG-A is Benign according to our data. Variant chr8-73976049-AGGCGGCAGGCGGGCGGCAGGCG-A is described in ClinVar as [Likely_benign]. Clinvar id is 1200878.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0164 (1698/103476) while in subpopulation SAS AF= 0.0238 (72/3020). AF 95% confidence interval is 0.0208. There are 22 homozygotes in gnomad4. There are 840 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 22 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	n.317+152_317+173del		intron_variant, non_coding_transcript_variant		2
TMEM70	ENST00000523794.1	n.574+152_575-171del		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.0165 AC: 1701 AN: 103388 Hom.: 22 Cov.: 0

Gnomad AFR AF: 0.00845

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0148

Gnomad ASJ AF: 0.0152

Gnomad EAS AF: 0.00660

Gnomad SAS AF: 0.0238

Gnomad FIN AF: 0.0263

Gnomad MID AF: 0.0124

Gnomad NFE AF: 0.0219

Gnomad OTH AF: 0.0146

GnomAD4 exome AF: 0.00836 AC: 1025 AN: 122558 Hom.: 51 AF XY: 0.00803 AC XY: 527 AN XY: 65590

Gnomad4 AFR exome AF: 0.00470

Gnomad4 AMR exome AF: 0.00215

Gnomad4 ASJ exome AF: 0.00645

Gnomad4 EAS exome AF: 0.00611

Gnomad4 SAS exome AF: 0.00144

Gnomad4 FIN exome AF: 0.0171

Gnomad4 NFE exome AF: 0.0107

Gnomad4 OTH exome AF: 0.00783

GnomAD4 genome AF: 0.0164 AC: 1698 AN: 103476 Hom.: 22 Cov.: 0 AF XY: 0.0167 AC XY: 840 AN XY: 50256

Gnomad4 AFR AF: 0.00839

Gnomad4 AMR AF: 0.0147

Gnomad4 ASJ AF: 0.0152

Gnomad4 EAS AF: 0.00664

Gnomad4 SAS AF: 0.0238

Gnomad4 FIN AF: 0.0263

Gnomad4 NFE AF: 0.0219

Gnomad4 OTH AF: 0.0145

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

Jun 16, 2018

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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;