rs12682285

Variant names:

• chr8-73975814-T-C
• rs12682285
• ENST00000520167.5:n.186-16T>C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000520167.5(TMEM70):​n.186-16T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.481 in 152,018 control chromosomes in the GnomAD database, including 17,728 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.48 (17728 hom., cov: 32)
  • Exomes 𝑓: 0.99 (2722 hom.)
  • Failed GnomAD Quality Control
• Consequence: TMEM70 ENST00000520167.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.05

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 8-73975814-T-C is Benign according to our data. Variant chr8-73975814-T-C is described in ClinVar as [Benign]. Clinvar id is 684008.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.533 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMEM70	ENST00000520167.5	n.186-16T>C		intron_variant	Intron 1 of 3	2
TMEM70	ENST00000523794.1	n.443-16T>C		intron_variant	Intron 1 of 2	3

Frequencies

GnomAD3 genomes AF: 0.481 AC: 73036 AN: 151900 Hom.: 17699 Cov.: 32

Gnomad AFR AF: 0.522

Gnomad AMI AF: 0.625

Gnomad AMR AF: 0.542

Gnomad ASJ AF: 0.432

Gnomad EAS AF: 0.317

Gnomad SAS AF: 0.512

Gnomad FIN AF: 0.475

Gnomad MID AF: 0.487

Gnomad NFE AF: 0.455

Gnomad OTH AF: 0.463

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.992 AC: 5484 AN: 5526 Hom.: 2722 Cov.: 0 AF XY: 0.992 AC XY: 2892 AN XY: 2914

Gnomad4 AFR exome AF: 1.00

Gnomad4 AMR exome AF: 0.998

Gnomad4 ASJ exome AF: 0.984

Gnomad4 EAS exome AF: 1.00

Gnomad4 SAS exome AF: 0.994

Gnomad4 FIN exome AF: 0.995

Gnomad4 NFE exome AF: 0.991

Gnomad4 OTH exome AF: 0.990

GnomAD4 genome AF: 0.481 AC: 73112 AN: 152018 Hom.: 17728 Cov.: 32 AF XY: 0.483 AC XY: 35885 AN XY: 74296

Gnomad4 AFR AF: 0.522

Gnomad4 AMR AF: 0.543

Gnomad4 ASJ AF: 0.432

Gnomad4 EAS AF: 0.315

Gnomad4 SAS AF: 0.511

Gnomad4 FIN AF: 0.475

Gnomad4 NFE AF: 0.454

Gnomad4 OTH AF: 0.463

Alfa AF: 0.460 Hom.: 16457

Bravo AF: 0.488

Asia WGS AF: 0.469 AC: 1630 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 14, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	3.9
DANN	Benign	0.60

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs12682285; hg19: chr8-74888049;