8-73976049-AGGCGGCAGGCGGGCGGCAGGCGGGCGGCAGGCGGGCGGCAGGCGGGCGGCAGGCGGGCGGCAGGCG-AGGCGGCAGGCGGGCGGCAGGCG

Variant names:

• chr8-73976049-AGGCGGCAGGCGGGCGGCAGGCGGGCGGCAGGCGGGCGGCAGGCG-A
• rs71269968
• ENST00000520167.5:n.317+89_317+132delGGCGGCAGGCGGGCGGCAGGCGGGCGGCAGGCGGGCGGCAGGCG

Variant summary

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

The ENST00000520167.5(TMEM70):​n.317+89_317+132delGGCGGCAGGCGGGCGGCAGGCGGGCGGCAGGCGGGCGGCAGGCG variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00499 in 226,214 control chromosomes in the GnomAD database, including 107 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0046 (3 hom., cov: 0)
  • Exomes 𝑓: 0.0053 (104 hom.)
• Consequence: TMEM70 ENST00000520167.5 intron
• Clinical Significance: Not reported in ClinVar
• 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: PanelApp Australia, Orphanet, G2P, Labcorp Genetics (formerly Invitae)
• 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 afr. GnomAd4 allele frequency = 0.00456 (472/103494) while in subpopulation AFR AF = 0.0119 (380/31820). AF 95% confidence interval is 0.011. There are 3 homozygotes in GnomAd4. There are 229 alleles in the male GnomAd4 subpopulation. Median coverage is 0. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 3 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.-232_-189delGGCGGCAGGCGGGCGGCAGGCGGGCGGCAGGCGGGCGGCAGGCG		upstream_gene	N/A	NP_060336.3
	TMEM70	NM_001040613.3		c.-232_-189delGGCGGCAGGCGGGCGGCAGGCGGGCGGCAGGCGGGCGGCAGGCG		upstream_gene	N/A	NP_001035703.1	Q9BUB7-3
	TMEM70	NR_033334.2		n.-145_-102delGGCGGCAGGCGGGCGGCAGGCGGGCGGCAGGCGGGCGGCAGGCG		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+132delGGCGGCAGGCGGGCGGCAGGCGGGCGGCAGGCGGGCGGCAGGCG		intron	N/A
	TMEM70	ENST00000523794.1	TSL:3	n.574+89_574+132delGGCGGCAGGCGGGCGGCAGGCGGGCGGCAGGCGGGCGGCAGGCG		intron	N/A
	TMEM70	ENST00000312184.6	TSL:1 MANE Select	c.-232_-189delGGCGGCAGGCGGGCGGCAGGCGGGCGGCAGGCGGGCGGCAGGCG		upstream_gene	N/A	ENSP00000312599.5	Q9BUB7-1

Frequencies

GnomAD3 genomes AF: 0.00455 AC: 470 AN: 103406 Hom.: 3 Cov.: 0

Gnomad AFR AF: 0.0120

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00161

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00330

Gnomad SAS AF: 0.0109

Gnomad FIN AF: 0.000529

Gnomad MID AF: 0.00826

Gnomad NFE AF: 0.000525

Gnomad OTH AF: 0.00146

GnomAD4 exome AF: 0.00535 AC: 656 AN: 122720 Hom.: 104 AF XY: 0.00606 AC XY: 398 AN XY: 65684

African (AFR) AF: 0.0120 AC: 59 AN: 4898

American (AMR) AF: 0.000858 AC: 8 AN: 9322

Ashkenazi Jewish (ASJ) AF: 0.000496 AC: 3 AN: 6046

East Asian (EAS) AF: 0.0328 AC: 188 AN: 5732

South Asian (SAS) AF: 0.0191 AC: 291 AN: 15248

European-Finnish (FIN) AF: 0.00151 AC: 10 AN: 6612

Middle Eastern (MID) AF: 0.00134 AC: 1 AN: 748

European-Non Finnish (NFE) AF: 0.00109 AC: 72 AN: 66178

Other (OTH) AF: 0.00302 AC: 24 AN: 7936

GnomAD4 genome AF: 0.00456 AC: 472 AN: 103494 Hom.: 3 Cov.: 0 AF XY: 0.00456 AC XY: 229 AN XY: 50258

African (AFR) AF: 0.0119 AC: 380 AN: 31820

American (AMR) AF: 0.00160 AC: 18 AN: 11232

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2770

East Asian (EAS) AF: 0.00332 AC: 10 AN: 3014

South Asian (SAS) AF: 0.0113 AC: 34 AN: 3016

European-Finnish (FIN) AF: 0.000529 AC: 3 AN: 5666

Middle Eastern (MID) AF: 0.00909 AC: 2 AN: 220

European-Non Finnish (NFE) AF: 0.000525 AC: 23 AN: 43824

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

Alfa AF: 0.00 Hom.: 39

ClinVar

Not reported in ClinVar

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs71269968;

hg19: chr8-74888284;