Variant 14-50116132-T-C 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_024558.3(VCPKMT):c.314A>G(p.Lys105Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000929 in 1,614,024 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000096 ( 0 hom. )

Consequence

VCPKMT
NM_024558.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.71

Variant links:

Genes affected

VCPKMT (HGNC:20352): (valosin containing protein lysine methyltransferase) Enables ATPase binding activity and protein-lysine N-methyltransferase activity. Involved in negative regulation of ATPase activity and peptidyl-lysine trimethylation. Located in cytosol. Part of protein-containing complex. [provided by Alliance of Genome Resources, Apr 2022]

VCPKMT links:

VCPKMT (HGNC:):

VCPKMT 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=0.1632852).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VCPKMT	NM_024558.3 linkuse as main transcript	c.314A>G	p.Lys105Arg	missense_variant	2/6	ENST00000395860.7	NP_078834.2	Q9H867-4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VCPKMT	ENST00000395860.7 linkuse as main transcript	c.314A>G	p.Lys105Arg	missense_variant	2/6	1	NM_024558.3	ENSP00000379201.2		Q9H867-4

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152222

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000958

AC:

AN:

1461802

Hom.:

Cov.:

AF XY:

0.0000124

AC XY:

AN XY:

727182

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:

0.0000126

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152222

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74370

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

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 02, 2024

The c.314A>G (p.K105R) alteration is located in exon 2 (coding exon 2) of the VCPKMT gene. This alteration results from a A to G substitution at nucleotide position 314, causing the lysine (K) at amino acid position 105 to be replaced by an arginine (R). 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

0.073

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.61

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0054

T;.

Eigen

Benign

-0.21

Eigen_PC

Benign

-0.049

FATHMM_MKL

Benign

0.76

LIST_S2

Benign

0.82

T;T

M_CAP

Benign

0.0041

MetaRNN

Benign

0.16

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.74

N;N

PrimateAI

Benign

0.34

PROVEAN

Benign

-1.3

N;N

REVEL

Benign

0.087

Sift

Benign

0.044

D;D

Sift4G

Benign

0.32

T;T

Polyphen

0.64

P;.

Vest4

0.15

MutPred

0.46

Gain of catalytic residue at N107 (P = 2e-04);Gain of catalytic residue at N107 (P = 2e-04);

MVP

0.33

MPC

0.0069

ClinPred

0.44

GERP RS

4.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.12

gMVP

0.48

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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