Variant 11-18534428-C-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_001040697.4(UEVLD):c.1150G>T(p.Gly384Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000184 in 1,574,508 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: 𝑓 0.00011 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000091 ( 0 hom. )

Consequence

UEVLD
NM_001040697.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.64

Variant links:

Genes affected

UEVLD (HGNC:30866): (UEV and lactate/malate dehyrogenase domains) Predicted to enable oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor. Predicted to be involved in several processes, including carbohydrate metabolic process; cellular protein modification process; and protein transport. Located in extracellular exosome. [provided by Alliance of Genome Resources, Apr 2022]

UEVLD links:

Genome browser will be placed here

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, 0.917

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UEVLD	NM_001040697.4 linkuse as main transcript	c.1150G>T	p.Gly384Cys	missense_variant	11/12	ENST00000396197.8	NP_001035787.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UEVLD	ENST00000396197.8 linkuse as main transcript	c.1150G>T	p.Gly384Cys	missense_variant	11/12	5	NM_001040697.4	ENSP00000379500	P1	Q8IX04-1

Frequencies

GnomAD3 genomes

AF:

0.000105

AC:

AN:

152122

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000386

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000332

AC:

AN:

210884

Hom.:

AF XY:

0.0000260

AC XY:

AN XY:

115572

show subpopulations

Gnomad AFR exome

AF:

0.000522

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:

0.00000914

AC:

AN:

1422386

Hom.:

Cov.:

AF XY:

0.00000708

AC XY:

AN XY:

706670

show subpopulations

Gnomad4 AFR exome

AF:

0.000388

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:

0.0000170

GnomAD4 genome

AF:

0.000105

AC:

AN:

152122

Hom.:

Cov.:

AF XY:

0.000135

AC XY:

AN XY:

74320

show subpopulations

Gnomad4 AFR

AF:

0.000386

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:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000214

Hom.:

Bravo

AF:

0.000136

ExAC

AF:

0.0000331

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 05, 2023

The c.1150G>T (p.G384C) alteration is located in exon 11 (coding exon 11) of the UEVLD gene. This alteration results from a G to T substitution at nucleotide position 1150, causing the glycine (G) at amino acid position 384 to be replaced by a cysteine (C). 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

0.34

BayesDel_addAF

Benign

-0.098

BayesDel_noAF

Uncertain

-0.020

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.61

D;.

Eigen

Benign

0.054

Eigen_PC

Benign

-0.067

FATHMM_MKL

Uncertain

0.84

LIST_S2

Uncertain

0.89

D;D

M_CAP

Uncertain

0.23

MetaRNN

Pathogenic

0.92

D;D

MetaSVM

Uncertain

0.12

MutationAssessor

Pathogenic

3.4

M;.

MutationTaster

Benign

1.0

D;D;D;D;D;D

PrimateAI

Benign

0.39

PROVEAN

Pathogenic

-7.8

D;D

REVEL

Uncertain

0.64

Sift

Uncertain

0.011

D;D

Sift4G

Pathogenic

0.0010

D;D

Polyphen

1.0

D;.

Vest4

0.64

MutPred

0.85

Gain of methylation at K383 (P = 0.0149);.;

MVP

0.88

MPC

0.47

ClinPred

0.97

GERP RS

2.8

Varity_R

0.83

gMVP

0.92

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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