ENST00000520167.5:n.186-16T>C

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 publications found

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

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM70	ENST00000520167.5	TSL:2	n.186-16T>C		intron	N/A
	TMEM70	ENST00000523794.1	TSL:3	n.443-16T>C		intron	N/A

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

African (AFR) AF: 1.00 AC: 138 AN: 138

American (AMR) AF: 0.998 AC: 533 AN: 534

Ashkenazi Jewish (ASJ) AF: 0.984 AC: 250 AN: 254

East Asian (EAS) AF: 1.00 AC: 62 AN: 62

South Asian (SAS) AF: 0.994 AC: 1058 AN: 1064

European-Finnish (FIN) AF: 0.995 AC: 217 AN: 218

Middle Eastern (MID) AF: 1.00 AC: 30 AN: 30

European-Non Finnish (NFE) AF: 0.991 AC: 2889 AN: 2916

Other (OTH) AF: 0.990 AC: 307 AN: 310

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

African (AFR) AF: 0.522 AC: 21638 AN: 41456

American (AMR) AF: 0.543 AC: 8291 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.432 AC: 1500 AN: 3470

East Asian (EAS) AF: 0.315 AC: 1629 AN: 5170

South Asian (SAS) AF: 0.511 AC: 2468 AN: 4826

European-Finnish (FIN) AF: 0.475 AC: 5015 AN: 10548

Middle Eastern (MID) AF: 0.473 AC: 139 AN: 294

European-Non Finnish (NFE) AF: 0.454 AC: 30885 AN: 67954

Other (OTH) AF: 0.463 AC: 978 AN: 2114

Alfa AF: 0.469 Hom.: 33399

Bravo AF: 0.488

Asia WGS AF: 0.469 AC: 1630 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	3.9
DANN	Benign	0.60
PhyloP100		-1.1
PromoterAI		0.036	Neutral

Splicing

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

Other links and lift over

dbSNP: rs12682285; hg19: chr8-74888049;