Variant 8-73976259-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_017866.6(TMEM70):c.-23C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.294 in 1,591,254 control chromosomes in the GnomAD database, including 71,399 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.25 ( 4999 hom., cov: 33)

Exomes 𝑓: 0.30 ( 66400 hom. )

Consequence

TMEM70
NM_017866.6 5_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -1.81

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.74).

BP6

Variant 8-73976259-C-T is Benign according to our data. Variant chr8-73976259-C-T is described in ClinVar as [Benign]. Clinvar id is 363687.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-73976259-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.299 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE
TMEM70	NM_017866.6 linkuse as main transcript	c.-23C>T	5_prime_UTR_variant	1/3	ENST00000312184.6
TMEM70	NM_001040613.3 linkuse as main transcript	c.-23C>T	5_prime_UTR_variant	1/3
TMEM70	NR_033334.2 linkuse as main transcript	n.65C>T	non_coding_transcript_exon_variant	1/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TMEM70	ENST00000312184.6 linkuse as main transcript	c.-23C>T		5_prime_UTR_variant	1/3	1	NM_017866.6	P1	Q9BUB7-1

Frequencies

GnomAD3 genomes

AF:

0.247

AC:

37474

AN:

152004

Hom.:

4996

Cov.:

show subpopulations

Gnomad AFR

AF:

0.148

Gnomad AMI

AF:

0.427

Gnomad AMR

AF:

0.228

Gnomad ASJ

AF:

0.132

Gnomad EAS

AF:

0.191

Gnomad SAS

AF:

0.303

Gnomad FIN

AF:

0.332

Gnomad MID

AF:

0.131

Gnomad NFE

AF:

0.302

Gnomad OTH

AF:

0.223

GnomAD3 exomes

AF:

0.272

AC:

60696

AN:

222958

Hom.:

8581

AF XY:

0.278

AC XY:

34110

AN XY:

122576

show subpopulations

Gnomad AFR exome

AF:

0.143

Gnomad AMR exome

AF:

0.261

Gnomad ASJ exome

AF:

0.130

Gnomad EAS exome

AF:

0.193

Gnomad SAS exome

AF:

0.318

Gnomad FIN exome

AF:

0.339

Gnomad NFE exome

AF:

0.302

Gnomad OTH exome

AF:

0.247

GnomAD4 exome

AF:

0.299

AC:

430213

AN:

1439132

Hom.:

66400

Cov.:

AF XY:

0.300

AC XY:

214856

AN XY:

716092

show subpopulations

Gnomad4 AFR exome

AF:

0.140

Gnomad4 AMR exome

AF:

0.256

Gnomad4 ASJ exome

AF:

0.127

Gnomad4 EAS exome

AF:

0.178

Gnomad4 SAS exome

AF:

0.320

Gnomad4 FIN exome

AF:

0.338

Gnomad4 NFE exome

AF:

0.312

Gnomad4 OTH exome

AF:

0.277

GnomAD4 genome

AF:

0.246

AC:

37488

AN:

152122

Hom.:

4999

Cov.:

AF XY:

0.247

AC XY:

18388

AN XY:

74374

show subpopulations

Gnomad4 AFR

AF:

0.148

Gnomad4 AMR

AF:

0.228

Gnomad4 ASJ

AF:

0.132

Gnomad4 EAS

AF:

0.190

Gnomad4 SAS

AF:

0.303

Gnomad4 FIN

AF:

0.332

Gnomad4 NFE

AF:

0.302

Gnomad4 OTH

AF:

0.223

Alfa

AF:

0.257

Hom.:

1621

Bravo

AF:

0.235

Asia WGS

AF:

0.237

AC:

826

AN:

3472

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -

Mitochondrial complex V (ATP synthase) deficiency nuclear type 2

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.74

CADD

Benign

5.7

DANN

Benign

0.93

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.2

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over