8-73976049-AGGCGGCAGGCGGGCGGCAGGCGGGCGGCAGGCGGGCGGCAGGCGGGCGGCAGGCGGGCGGCAGGCG-AGGCGGCAGGCGGGCGGCAGGCGGGCGGCAGGCGGGCGGCAGGCGGGCGGCAGGCGGGCGGCAGGCGGGCGGCAGGCGGGCGGCAGGCGGGCGGCAGGCGGGCGGCAGGCG

Variant names:

• chr8-73976049-A-AGGCGGCAGGCGGGCGGCAGGCGGGCGGCAGGCGGGCGGCAGGCG
• rs71269968
• ENST00000520167.5:n.317+88_317+89insGGCGGCAGGCGGGCGGCAGGCGGGCGGCAGGCGGGCGGCAGGCG

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BS1 BS2

The ENST00000520167.5(TMEM70):​n.317+88_317+89insGGCGGCAGGCGGGCGGCAGGCGGGCGGCAGGCGGGCGGCAGGCG variant causes a intron change involving the alteration of a non-conserved nucleotide. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0042 (60 hom., cov: 0)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: TMEM70 ENST00000520167.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.111
• Publications: 1 publications found

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 Gene-Disease associations (from GenCC):

• mitochondrial complex V (ATP synthase) deficiency, nuclear type 2

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Labcorp Genetics (formerly Invitae), Orphanet
• mitochondrial disease

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BS1: Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.00422 (437/103498) while in subpopulation EAS AF = 0.00963 (29/3012). AF 95% confidence interval is 0.00689. There are 60 homozygotes in GnomAd4. There are 186 alleles in the male GnomAd4 subpopulation. Median coverage is 0. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 60 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000520167.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM70	NM_017866.6	MANE Select	c.-233_-232insGGCGGCAGGCGGGCGGCAGGCGGGCGGCAGGCGGGCGGCAGGCG		upstream_gene	N/A	NP_060336.3
	TMEM70	NM_001040613.3		c.-233_-232insGGCGGCAGGCGGGCGGCAGGCGGGCGGCAGGCGGGCGGCAGGCG		upstream_gene	N/A	NP_001035703.1	Q9BUB7-3
	TMEM70	NR_033334.2		n.-146_-145insGGCGGCAGGCGGGCGGCAGGCGGGCGGCAGGCGGGCGGCAGGCG		upstream_gene	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM70	ENST00000520167.5	TSL:2	n.317+88_317+89insGGCGGCAGGCGGGCGGCAGGCGGGCGGCAGGCGGGCGGCAGGCG		intron	N/A
	TMEM70	ENST00000523794.1	TSL:3	n.574+88_574+89insGGCGGCAGGCGGGCGGCAGGCGGGCGGCAGGCGGGCGGCAGGCG		intron	N/A
	TMEM70	ENST00000312184.6	TSL:1 MANE Select	c.-233_-232insGGCGGCAGGCGGGCGGCAGGCGGGCGGCAGGCGGGCGGCAGGCG		upstream_gene	N/A	ENSP00000312599.5	Q9BUB7-1

Frequencies

GnomAD3 genomes AF: 0.00425 AC: 440 AN: 103410 Hom.: 62 Cov.: 0

Gnomad AFR AF: 0.00211

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00241

Gnomad ASJ AF: 0.00217

Gnomad EAS AF: 0.0102

Gnomad SAS AF: 0.00463

Gnomad FIN AF: 0.00406

Gnomad MID AF: 0.00413

Gnomad NFE AF: 0.00614

Gnomad OTH AF: 0.00146

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 122740 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 65694

African (AFR) AF: 0.00 AC: 0 AN: 4898

American (AMR) AF: 0.00 AC: 0 AN: 9322

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 6046

East Asian (EAS) AF: 0.00 AC: 0 AN: 5732

South Asian (SAS) AF: 0.00 AC: 0 AN: 15264

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6612

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 748

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 66182

Other (OTH) AF: 0.00 AC: 0 AN: 7936

GnomAD4 genome AF: 0.00422 AC: 437 AN: 103498 Hom.: 60 Cov.: 0 AF XY: 0.00370 AC XY: 186 AN XY: 50264

African (AFR) AF: 0.00211 AC: 67 AN: 31822

American (AMR) AF: 0.00240 AC: 27 AN: 11232

Ashkenazi Jewish (ASJ) AF: 0.00217 AC: 6 AN: 2770

East Asian (EAS) AF: 0.00963 AC: 29 AN: 3012

South Asian (SAS) AF: 0.00464 AC: 14 AN: 3020

European-Finnish (FIN) AF: 0.00406 AC: 23 AN: 5666

Middle Eastern (MID) AF: 0.00455 AC: 1 AN: 220

European-Non Finnish (NFE) AF: 0.00612 AC: 268 AN: 43824

Other (OTH) AF: 0.00145 AC: 2 AN: 1380

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.11

Splicing

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

Other links and lift over

dbSNP: rs71269968; hg19: chr8-74888284;