Variant chr14-50116334-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 4P and 1B. PM1PM2BP4

The NM_024558.3(VCPKMT):c.219G>C(p.Glu73Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000559 in 1,610,952 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

VCPKMT
NM_024558.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.23

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 3 ACMG points.

PM1

In a mutagenesis_site Loss of methyltransferase activity. (size 0) in uniprot entity MT21D_HUMAN

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.30092275).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VCPKMT	NM_024558.3 linkuse as main transcript	c.219G>C	p.Glu73Asp	missense_variant	1/6	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.219G>C	p.Glu73Asp	missense_variant	1/6	1	NM_024558.3	ENSP00000379201.2		Q9H867-4

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152178

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:

0.000385

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:

0.0000750

AC:

AN:

240152

Hom.:

AF XY:

0.0000914

AC XY:

AN XY:

131252

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00101

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:

0.00000480

AC:

AN:

1458774

Hom.:

Cov.:

AF XY:

0.00000827

AC XY:

AN XY:

725500

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000177

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152178

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74340

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000385

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000189

ExAC

AF:

0.000115

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

Aug 01, 2024

The c.219G>C (p.E73D) alteration is located in exon 1 (coding exon 1) of the VCPKMT gene. This alteration results from a G to C substitution at nucleotide position 219, causing the glutamic acid (E) at amino acid position 73 to be replaced by an aspartic acid (D). 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

0.87

BayesDel_addAF

Benign

-0.078

BayesDel_noAF

Uncertain

0.050

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.11

T;.

Eigen

Benign

-0.059

Eigen_PC

Benign

-0.0045

FATHMM_MKL

Benign

0.51

LIST_S2

Uncertain

0.91

D;D

M_CAP

Benign

0.0095

MetaRNN

Benign

0.30

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Pathogenic

3.2

M;M

PrimateAI

Uncertain

0.76

PROVEAN

Uncertain

-2.6

D;D

REVEL

Benign

0.25

Sift

Benign

0.048

D;D

Sift4G

Uncertain

0.036

D;D

Polyphen

0.41

B;.

Vest4

0.94

MutPred

0.78

Gain of catalytic residue at T78 (P = 0);Gain of catalytic residue at T78 (P = 0);

MVP

0.28

MPC

0.018

ClinPred

0.49

GERP RS

1.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.91

gMVP

0.94

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