8-73975814-T-C

Position:

• chr8-73975814-T-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 splice polypyrimidine tract, intron, non coding transcript 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 splice_polypyrimidine_tract, intron, non_coding_transcript
• 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/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMEM70	ENST00000520167.5	n.186-16T>C		splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant		2
TMEM70	ENST00000523794.1	n.443-16T>C		splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant		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

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 14, 2018	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;