Variant chr11-18558329-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001040697.4(UEVLD):c.614G>A(p.Gly205Asp) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000484 in 1,445,440 control chromosomes in the GnomAD database, with no homozygous occurrence. 14/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

UEVLD
NM_001040697.4 missense, splice_region

Scores

Splicing: ADA: 0.0001548

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

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 Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UEVLD	NM_001040697.4 linkuse as main transcript	c.614G>A	p.Gly205Asp	missense_variant, splice_region_variant	7/12	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.614G>A	p.Gly205Asp	missense_variant, splice_region_variant	7/12	5	NM_001040697.4	ENSP00000379500	P1	Q8IX04-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000824

AC:

AN:

242672

Hom.:

AF XY:

0.0000152

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:

0.0000699

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000484

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:

0.0000718

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000167

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ExAC

AF:

0.00000824

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

May 11, 2022

The c.614G>A (p.G205D) alteration is located in exon 7 (coding exon 7) of the UEVLD gene. This alteration results from a G to A substitution at nucleotide position 614, causing the glycine (G) at amino acid position 205 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

Benign

0.15

BayesDel_addAF

Benign

-0.011

BayesDel_noAF

Benign

-0.15

CADD

Benign

DANN

Benign

0.42

DEOGEN2

Benign

0.22

T;.;.;.;.;.

Eigen

Benign

-0.34

Eigen_PC

Benign

-0.22

FATHMM_MKL

Uncertain

0.86

LIST_S2

Benign

0.80

T;T;T;T;T;T

M_CAP

Uncertain

0.10

MetaRNN

Uncertain

0.54

D;D;D;D;D;D

MetaSVM

Benign

-0.31

MutationAssessor

Benign

1.2

L;L;.;.;.;.

MutationTaster

Benign

1.0

D;D;D;D;D;D

PrimateAI

Uncertain

0.56

PROVEAN

Benign

-1.1

N;N;N;N;N;N

REVEL

Uncertain

0.37

Sift

Benign

0.55

T;T;T;T;T;T

Sift4G

Benign

0.80

T;T;T;T;T;T

Polyphen

0.0050

B;B;.;B;.;.

Vest4

0.49

MutPred

0.82

Gain of solvent accessibility (P = 0.1045);Gain of solvent accessibility (P = 0.1045);.;.;.;.;

MVP

0.87

MPC

0.45

ClinPred

0.14

GERP RS

4.5

Varity_R

0.20

gMVP

0.43

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00015

dbscSNV1_RF

Benign

0.062

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