Genetic Variant TMEM70:n.317+57C>A (chr8-73976018-C-A) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000520167.5(TMEM70):n.317+57C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0681 in 241,456 control chromosomes in the GnomAD database, including 6,168 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.018 ( 40 hom., cov: 33)

Exomes 𝑓: 0.15 ( 6128 hom. )

Consequence

TMEM70
ENST00000520167.5 intron

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.853

Publications

0 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: Orphanet, PanelApp Australia, G2P, Labcorp Genetics (formerly Invitae)
mitochondrial disease
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen

TMEM70 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 8-73976018-C-A is Benign according to our data. Variant chr8-73976018-C-A is described in ClinVar as Likely_benign. ClinVar VariationId is 676048.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAdExome4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.174 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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
TMEM70	NM_017866.6	MANE Select	c.-264C>A	upstream_gene	N/A	NP_060336.3
TMEM70	NM_001040613.3		c.-264C>A	upstream_gene	N/A	NP_001035703.1	Q9BUB7-3
TMEM70	NR_033334.2		n.-177C>A	upstream_gene	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
TMEM70	ENST00000520167.5	TSL:2	n.317+57C>A	intron	N/A
TMEM70	ENST00000523794.1	TSL:3	n.574+57C>A	intron	N/A
TMEM70	ENST00000312184.6	TSL:1 MANE Select	c.-264C>A	upstream_gene	N/A	ENSP00000312599.5	Q9BUB7-1

Frequencies

GnomAD3 genomes

AF:

0.0179

AC:

2625

AN:

146940

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00653

Gnomad AMI

AF:

0.00341

Gnomad AMR

AF:

0.0132

Gnomad ASJ

AF:

0.0228

Gnomad EAS

AF:

0.0158

Gnomad SAS

AF:

0.0357

Gnomad FIN

AF:

0.0505

Gnomad MID

AF:

0.0226

Gnomad NFE

AF:

0.0198

Gnomad OTH

AF:

0.0181

GnomAD4 exome

AF:

0.146

AC:

13813

AN:

94410

Hom.:

6128

Cov.:

AF XY:

0.149

AC XY:

7684

AN XY:

51540

show subpopulations

African (AFR)

AF:

0.0290

AC:

104

AN:

3586

American (AMR)

AF:

0.0503

AC:

345

AN:

6858

Ashkenazi Jewish (ASJ)

AF:

0.0956

AC:

412

AN:

4308

East Asian (EAS)

AF:

0.147

AC:

487

AN:

3322

South Asian (SAS)

AF:

0.180

AC:

2722

AN:

15114

European-Finnish (FIN)

AF:

0.341

AC:

1668

AN:

4894

Middle Eastern (MID)

AF:

0.151

AC:

AN:

558

European-Non Finnish (NFE)

AF:

0.145

AC:

7240

AN:

49918

Other (OTH)

AF:

0.128

AC:

751

AN:

5852

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.548

Heterozygous variant carriers

146

219

292

365

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

112

140

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0179

AC:

2634

AN:

147046

Hom.:

Cov.:

AF XY:

0.0196

AC XY:

1405

AN XY:

71812

show subpopulations

African (AFR)

AF:

0.00669

AC:

270

AN:

40388

American (AMR)

AF:

0.0131

AC:

194

AN:

14764

Ashkenazi Jewish (ASJ)

AF:

0.0228

AC:

AN:

3422

East Asian (EAS)

AF:

0.0158

AC:

AN:

4868

South Asian (SAS)

AF:

0.0357

AC:

166

AN:

4654

European-Finnish (FIN)

AF:

0.0505

AC:

496

AN:

9824

Middle Eastern (MID)

AF:

0.0243

AC:

AN:

288

European-Non Finnish (NFE)

AF:

0.0198

AC:

1304

AN:

65896

Other (OTH)

AF:

0.0189

AC:

AN:

2062

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

118

235

353

470

588

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

108

144

180

<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:

0.00880

Hom.:

Bravo

AF:

0.0144

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

2.3

(source)

DANN

Benign

0.64

PhyloP100

-0.85

PromoterAI

0.087

Neutral

(source)

Splicing

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over