Genetic Variant TMEM70:n.317+88_317+89insGGCGGCAGGCGGGCGGCAGGCGGGCGGCAGGCG (chr8-73976049-A-AGGCGGCAGGCGGGCGGCAGGCGGGCGGCAGGCG) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_ModerateBS1BS2

The ENST00000520167.5(TMEM70):n.317+88_317+89insGGCGGCAGGCGGGCGGCAGGCGGGCGGCAGGCG 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. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.026 ( 340 hom., cov: 0)

Consequence

TMEM70
ENST00000520167.5 intron

Scores

Not classified

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.111

Publications

1 publications found

Variant links:

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

TMEM70 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId 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 the male GnomAd4 subpopulation. Median coverage is 0. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 340 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

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

Ensembl Transcripts

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

Frequencies

GnomAD3 genomes

AF:

0.0263

AC:

2723

AN:

103386

Hom.:

341

Cov.:

show subpopulations

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.:

GnomAD4 genome

AF:

0.0263

AC:

2726

AN:

103474

Hom.:

340

Cov.:

AF XY:

0.0251

AC XY:

1260

AN XY:

50248

show subpopulations

African (AFR)

AF:

0.0185

AC:

589

AN:

31812

American (AMR)

AF:

0.0257

AC:

289

AN:

11234

Ashkenazi Jewish (ASJ)

AF:

0.0141

AC:

AN:

2770

East Asian (EAS)

AF:

0.0428

AC:

129

AN:

3014

South Asian (SAS)

AF:

0.0186

AC:

AN:

3018

European-Finnish (FIN)

AF:

0.0279

AC:

158

AN:

5666

Middle Eastern (MID)

AF:

0.00455

AC:

AN:

220

European-Non Finnish (NFE)

AF:

0.0320

AC:

1400

AN:

43810

Other (OTH)

AF:

0.0189

AC:

AN:

1378

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

156

235

313

391

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

104

130

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00247

Hom.:

ClinVar

ClinVar submissions as Germline

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

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

Publications

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8-73976049-AGGCGGCAGGCGGGCGGCAGGCGGGCGGCAGGCGGGCGGCAGGCGGGCGGCAGGCGGGCGGCAGGCG-AGGCGGCAGGCGGGCGGCAGGCGGGCGGCAGGCGGGCGGCAGGCGGGCGGCAGGCGGGCGGCAGGCGGGCGGCAGGCGGGCGGCAGGCGGGCGGCAGGCG

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over