Variant chr10-103392445-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001206427.2(ATP5MK):c.13G>C(p.Glu5Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000025 in 1,598,694 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00015 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

ATP5MK
NM_001206427.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.49

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 Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.13111183).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
ATP5MK	NM_001206427.2 linkuse as main transcript	c.13G>C	p.Glu5Gln	missense_variant	3/5	ENST00000369815.6	NP_001193356.1
ATP5MK	NM_001206426.2 linkuse as main transcript	c.13G>C	p.Glu5Gln	missense_variant	2/4		NP_001193355.1
ATP5MK	NM_032747.4 linkuse as main transcript	c.13G>C	p.Glu5Gln	missense_variant	3/5		NP_116136.1
ATP5MK	XM_024448237.2 linkuse as main transcript	c.13G>C	p.Glu5Gln	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.13G>C	p.Glu5Gln	missense_variant	3/5	2	NM_001206427.2	ENSP00000358830	P1

Frequencies

GnomAD3 genomes

AF:

0.000151

AC:

AN:

152052

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000532

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000298

AC:

AN:

234932

Hom.:

AF XY:

0.0000235

AC XY:

AN XY:

127538

show subpopulations

Gnomad AFR exome

AF:

0.000468

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000118

AC:

AN:

1446642

Hom.:

Cov.:

AF XY:

0.00000417

AC XY:

AN XY:

719238

show subpopulations

Gnomad4 AFR exome

AF:

0.000490

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000167

GnomAD4 genome

AF:

0.000151

AC:

AN:

152052

Hom.:

Cov.:

AF XY:

0.000148

AC XY:

AN XY:

74244

show subpopulations

Gnomad4 AFR

AF:

0.000532

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.000106

ESP6500AA

AF:

0.000229

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000165

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

Mar 04, 2024

The c.13G>C (p.E5Q) alteration is located in exon 3 (coding exon 1) of the USMG5 gene. This alteration results from a G to C substitution at nucleotide position 13, causing the glutamic acid (E) at amino acid position 5 to be replaced by a glutamine (Q). 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

0.23

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.32

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.021

T;T;T;T;T

Eigen

Uncertain

0.58

Eigen_PC

Uncertain

0.60

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.74

.;.;.;.;T

M_CAP

Benign

0.040

MetaRNN

Benign

0.13

T;T;T;T;T

MetaSVM

Benign

-0.43

MutationTaster

Benign

1.0

D;D;D;D;D

PrimateAI

Uncertain

0.60

PROVEAN

Benign

-1.1

N;N;N;N;N

REVEL

Benign

0.19

Sift

Uncertain

0.014

D;D;D;D;D

Sift4G

Benign

0.085

T;T;T;T;T

Polyphen

0.93

P;P;P;P;P

Vest4

0.23

MVP

0.055

MPC

0.11

ClinPred

0.67

GERP RS

6.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.17

gMVP

0.30

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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