Variant 10-103392390-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_001206427.2(ATP5MK):c.68C>T(p.Thr23Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000687 in 1,454,712 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

ATP5MK
NM_001206427.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.62

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.851

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATP5MK	NM_001206427.2 linkuse as main transcript	c.68C>T	p.Thr23Ile	missense_variant	3/5	ENST00000369815.6	NP_001193356.1	Q96IX5
ATP5MK	NM_001206426.2 linkuse as main transcript	c.68C>T	p.Thr23Ile	missense_variant	2/4		NP_001193355.1	Q96IX5
ATP5MK	NM_032747.4 linkuse as main transcript	c.68C>T	p.Thr23Ile	missense_variant	3/5		NP_116136.1	Q96IX5
ATP5MK	XM_024448237.2 linkuse as main transcript	c.68C>T	p.Thr23Ile	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.68C>T	p.Thr23Ile	missense_variant	3/5	2	NM_001206427.2	ENSP00000358830.1		Q96IX5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.87e-7

AC:

AN:

1454712

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

723332

show subpopulations

Gnomad4 AFR exome

AF:

0.00

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:

9.01e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Oct 02, 2023

The c.68C>T (p.T23I) 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 68, causing the threonine (T) at amino acid position 23 to be replaced by an isoleucine (I). 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

Pathogenic

0.99

BayesDel_addAF

Pathogenic

0.46

BayesDel_noAF

Pathogenic

0.42

CADD

Uncertain

DANN

Benign

0.80

DEOGEN2

Uncertain

0.44

T;T;T;T;T

Eigen

Pathogenic

0.75

Eigen_PC

Pathogenic

0.74

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.77

.;.;.;.;T

M_CAP

Uncertain

0.12

MetaRNN

Pathogenic

0.85

D;D;D;D;D

MetaSVM

Uncertain

0.033

PrimateAI

Uncertain

0.77

PROVEAN

Pathogenic

-6.0

D;D;D;D;D

REVEL

Uncertain

0.62

Sift

Uncertain

0.021

D;D;D;D;D

Sift4G

Uncertain

0.058

T;T;T;T;T

Polyphen

1.0

D;D;D;D;D

Vest4

0.97

MutPred

0.36

Gain of helix (P = 0.0696);Gain of helix (P = 0.0696);Gain of helix (P = 0.0696);Gain of helix (P = 0.0696);Gain of helix (P = 0.0696);

MVP

0.19

MPC

0.021

ClinPred

0.62

GERP RS

6.2

RBP_binding_hub_radar

0.92

RBP_regulation_power_radar

2.7

Varity_R

0.46

gMVP

0.84

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over