dbSNP rs765156441: UEVLD:p.Gly205Val (chr11-18558329-C-A) – ACMG Classification: Likely_pathogenic (6 pts)

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_001040697.4(UEVLD):c.614G>T(p.Gly205Val) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000083 in 1,445,440 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G205D) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000083 ( 0 hom. )

Consequence

UEVLD
NM_001040697.4 missense, splice_region

Scores

Splicing: ADA: 0.0004856

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.78

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:

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ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.942

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UEVLD	NM_001040697.4 link	c.614G>T	p.Gly205Val	missense_variant, splice_region_variant	Exon 7 of 12	ENST00000396197.8	NP_001035787.1	Q8IX04-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UEVLD	ENST00000396197.8 link	c.614G>T	p.Gly205Val	missense_variant, splice_region_variant	Exon 7 of 12	5	NM_001040697.4	ENSP00000379500.2		Q8IX04-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000330

AC:

AN:

242672

Hom.:

AF XY:

0.0000229

AC XY:

AN XY:

131244

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000280

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000830

AC:

AN:

1445440

Hom.:

Cov.:

AF XY:

0.00000695

AC XY:

AN XY:

718998

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:

0.000132

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000167

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000247

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.41

BayesDel_addAF

Benign

-0.029

BayesDel_noAF

Uncertain

0.020

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Uncertain

0.77

D;.;.;.;.;.

Eigen

Benign

0.091

Eigen_PC

Benign

0.090

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.76

T;T;T;T;T;T

M_CAP

Pathogenic

0.34

MetaRNN

Pathogenic

0.94

D;D;D;D;D;D

MetaSVM

Uncertain

0.49

MutationAssessor

Pathogenic

3.0

M;M;.;.;.;.

PrimateAI

Benign

0.48

PROVEAN

Uncertain

-4.3

D;D;D;D;D;D

REVEL

Pathogenic

0.66

Sift

Uncertain

0.0010

D;D;D;D;D;D

Sift4G

Uncertain

0.042

D;D;D;D;D;T

Polyphen

0.29

B;B;.;P;.;.

Vest4

0.75

MutPred

0.81

Gain of ubiquitination at K204 (P = 0.0719);Gain of ubiquitination at K204 (P = 0.0719);.;.;.;.;

MVP

0.96

MPC

0.51

ClinPred

0.65

GERP RS

4.5

Varity_R

0.58

gMVP

0.60

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00049

dbscSNV1_RF

Benign

0.0020

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over