Variant 10-103392435-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001206427.2(ATP5MK):c.23C>T(p.Ala8Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000368 in 1,603,294 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000086 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000032 ( 0 hom. )

Consequence

ATP5MK
NM_001206427.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.58

Variant links:

Genes affected

ATP5MK (HGNC:30889): (ATP synthase membrane subunit k) Located in mitochondrion. Part of mitochondrial proton-transporting ATP synthase complex. Implicated in mitochondrial complex V (ATP synthase) deficiency nuclear type 6. [provided by Alliance of Genome Resources, Apr 2022]

ATP5MK links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.02137795).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATP5MK	NM_001206427.2 linkuse as main transcript	c.23C>T	p.Ala8Val	missense_variant	3/5	ENST00000369815.6	NP_001193356.1	Q96IX5
ATP5MK	NM_001206426.2 linkuse as main transcript	c.23C>T	p.Ala8Val	missense_variant	2/4		NP_001193355.1	Q96IX5
ATP5MK	NM_032747.4 linkuse as main transcript	c.23C>T	p.Ala8Val	missense_variant	3/5		NP_116136.1	Q96IX5
ATP5MK	XM_024448237.2 linkuse as main transcript	c.23C>T	p.Ala8Val	missense_variant	4/6		XP_024304005.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ATP5MK	ENST00000369815.6 linkuse as main transcript	c.23C>T	p.Ala8Val	missense_variant	3/5	2	NM_001206427.2	ENSP00000358830.1		Q96IX5

Frequencies

GnomAD3 genomes

AF:

0.0000856

AC:

AN:

151934

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000726

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000394

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.000386

Gnomad SAS

AF:

0.000208

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000113

AC:

AN:

239968

Hom.:

AF XY:

0.0000922

AC XY:

AN XY:

130098

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000377

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000618

Gnomad SAS exome

AF:

0.0000725

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000905

Gnomad OTH exome

AF:

0.000171

GnomAD4 exome

AF:

0.0000317

AC:

AN:

1451360

Hom.:

Cov.:

AF XY:

0.0000263

AC XY:

AN XY:

721782

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000401

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000279

Gnomad4 SAS exome

AF:

0.0000359

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000117

Gnomad4 OTH exome

AF:

0.0000334

GnomAD4 genome

AF:

0.0000856

AC:

AN:

151934

Hom.:

Cov.:

AF XY:

0.000108

AC XY:

AN XY:

74180

show subpopulations

Gnomad4 AFR

AF:

0.0000726

Gnomad4 AMR

AF:

0.000394

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.000208

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000604

ExAC

AF:

0.0000660

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 20, 2021

The c.23C>T (p.A8V) alteration is located in exon 3 (coding exon 1) of the USMG5 gene. This alteration results from a C to T substitution at nucleotide position 23, causing the alanine (A) at amino acid position 8 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.56

CADD

Benign

DANN

Benign

0.79

DEOGEN2

Benign

0.015

T;T;T;T;T

Eigen

Benign

-0.64

Eigen_PC

Benign

-0.56

FATHMM_MKL

Benign

0.36

LIST_S2

Benign

0.54

.;.;.;.;T

M_CAP

Benign

0.0045

MetaRNN

Benign

0.021

T;T;T;T;T

MetaSVM

Benign

-1.0

PrimateAI

Benign

0.44

PROVEAN

Benign

-1.5

N;N;N;N;N

REVEL

Benign

0.13

Sift

Benign

0.090

T;T;T;T;T

Sift4G

Benign

0.14

T;T;T;T;T

Polyphen

0.013

B;B;B;B;B

Vest4

0.17

MutPred

0.14

Loss of helix (P = 0.0196);Loss of helix (P = 0.0196);Loss of helix (P = 0.0196);Loss of helix (P = 0.0196);Loss of helix (P = 0.0196);

MVP

0.014

MPC

0.023

ClinPred

0.020

GERP RS

3.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.032

gMVP

0.35

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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