chr8-73976049-AGGCGGCAGGCGGGCGGCAGGCGGGCGGCAGGCGGGCGGCAGGCGGGCGGCAGGCG-A

Variant names:

• chr8-73976049-AGGCGGCAGGCGGGCGGCAGGCGGGCGGCAGGCGGGCGGCAGGCGGGCGGCAGGCG-A
• rs71269968
• ENST00000520167.5:n.317+89_317+143delGGCGGCAGGCGGGCGGCAGGCGGGCGGCAGGCGGGCGGCAGGCGGGCGGCAGGCG

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The ENST00000520167.5(TMEM70):​n.317+89_317+143delGGCGGCAGGCGGGCGGCAGGCGGGCGGCAGGCGGGCGGCAGGCGGGCGGCAGGCG variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.527 in 225,888 control chromosomes in the GnomAD database, including 32,608 homozygotes. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.33 (4754 hom., cov: 0)
  • Exomes 𝑓: 0.70 (27854 hom.)
• Consequence: TMEM70 ENST00000520167.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.351
• 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: Orphanet, PanelApp Australia, G2P, Labcorp Genetics (formerly Invitae)
• mitochondrial disease

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP6: Variant 8-73976049-AGGCGGCAGGCGGGCGGCAGGCGGGCGGCAGGCGGGCGGCAGGCGGGCGGCAGGCG-A is Benign according to our data. Variant chr8-73976049-AGGCGGCAGGCGGGCGGCAGGCGGGCGGCAGGCGGGCGGCAGGCGGGCGGCAGGCG-A is described in ClinVar as Benign. ClinVar VariationId is 1248803.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.452 is higher than 0.05.

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.-232_-178delGGCGGCAGGCGGGCGGCAGGCGGGCGGCAGGCGGGCGGCAGGCGGGCGGCAGGCG		upstream_gene	N/A	NP_060336.3
	TMEM70	NM_001040613.3		c.-232_-178delGGCGGCAGGCGGGCGGCAGGCGGGCGGCAGGCGGGCGGCAGGCGGGCGGCAGGCG		upstream_gene	N/A	NP_001035703.1	Q9BUB7-3
	TMEM70	NR_033334.2		n.-145_-91delGGCGGCAGGCGGGCGGCAGGCGGGCGGCAGGCGGGCGGCAGGCGGGCGGCAGGCG		upstream_gene	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM70	ENST00000520167.5	TSL:2	n.317+89_317+143delGGCGGCAGGCGGGCGGCAGGCGGGCGGCAGGCGGGCGGCAGGCGGGCGGCAGGCG		intron	N/A
	TMEM70	ENST00000523794.1	TSL:3	n.574+89_574+143delGGCGGCAGGCGGGCGGCAGGCGGGCGGCAGGCGGGCGGCAGGCGGGCGGCAGGCG		intron	N/A
	TMEM70	ENST00000312184.6	TSL:1 MANE Select	c.-232_-178delGGCGGCAGGCGGGCGGCAGGCGGGCGGCAGGCGGGCGGCAGGCGGGCGGCAGGCG		upstream_gene	N/A	ENSP00000312599.5	Q9BUB7-1

Frequencies

GnomAD3 genomes AF: 0.326 AC: 33615 AN: 103110 Hom.: 4740 Cov.: 0

Gnomad AFR AF: 0.458

Gnomad AMI AF: 0.305

Gnomad AMR AF: 0.411

Gnomad ASJ AF: 0.370

Gnomad EAS AF: 0.205

Gnomad SAS AF: 0.303

Gnomad FIN AF: 0.237

Gnomad MID AF: 0.417

Gnomad NFE AF: 0.227

Gnomad OTH AF: 0.347

GnomAD4 exome AF: 0.696 AC: 85450 AN: 122690 Hom.: 27854 AF XY: 0.702 AC XY: 46091 AN XY: 65664

African (AFR) AF: 0.636 AC: 3111 AN: 4894

American (AMR) AF: 0.749 AC: 6979 AN: 9316

Ashkenazi Jewish (ASJ) AF: 0.693 AC: 4191 AN: 6046

East Asian (EAS) AF: 0.557 AC: 3195 AN: 5732

South Asian (SAS) AF: 0.862 AC: 13141 AN: 15238

European-Finnish (FIN) AF: 0.649 AC: 4291 AN: 6612

Middle Eastern (MID) AF: 0.693 AC: 517 AN: 746

European-Non Finnish (NFE) AF: 0.675 AC: 44670 AN: 66170

Other (OTH) AF: 0.675 AC: 5355 AN: 7936

GnomAD4 genome AF: 0.326 AC: 33668 AN: 103198 Hom.: 4754 Cov.: 0 AF XY: 0.329 AC XY: 16480 AN XY: 50124

African (AFR) AF: 0.458 AC: 14506 AN: 31658

American (AMR) AF: 0.412 AC: 4620 AN: 11220

Ashkenazi Jewish (ASJ) AF: 0.370 AC: 1021 AN: 2762

East Asian (EAS) AF: 0.203 AC: 612 AN: 3008

South Asian (SAS) AF: 0.302 AC: 910 AN: 3012

European-Finnish (FIN) AF: 0.237 AC: 1343 AN: 5656

Middle Eastern (MID) AF: 0.409 AC: 90 AN: 220

European-Non Finnish (NFE) AF: 0.227 AC: 9919 AN: 43736

Other (OTH) AF: 0.348 AC: 479 AN: 1376

Alfa AF: 0.0625 Hom.: 39

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.35

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;