Variant chr11-18534418-G-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.1160C>T(p.Ser387Phe) variant causes a missense change. The variant allele was found at a frequency of 0.0000742 in 1,576,954 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 0.000039 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000078 ( 0 hom. )

Consequence

UEVLD
NM_001040697.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.87

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, 0.875

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UEVLD	NM_001040697.4 linkuse as main transcript	c.1160C>T	p.Ser387Phe	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.1160C>T	p.Ser387Phe	missense_variant	11/12	5	NM_001040697.4	ENSP00000379500	P1	Q8IX04-1

Frequencies

GnomAD3 genomes

AF:

0.0000394

AC:

AN:

152106

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

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:

0.0000735

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000468

AC:

AN:

213540

Hom.:

AF XY:

0.0000513

AC XY:

AN XY:

116948

show subpopulations

Gnomad AFR exome

AF:

0.0000736

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:

0.0000873

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000779

AC:

111

AN:

1424848

Hom.:

Cov.:

AF XY:

0.0000692

AC XY:

AN XY:

707894

show subpopulations

Gnomad4 AFR exome

AF:

0.0000321

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:

0.0000954

Gnomad4 OTH exome

AF:

0.0000847

GnomAD4 genome

AF:

0.0000394

AC:

AN:

152106

Hom.:

Cov.:

AF XY:

0.0000538

AC XY:

AN XY:

74318

show subpopulations

Gnomad4 AFR

AF:

0.0000241

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:

0.0000735

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000155

Hom.:

Bravo

AF:

0.0000567

ExAC

AF:

0.0000414

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

Mar 29, 2023

The c.1160C>T (p.S387F) alteration is located in exon 11 (coding exon 11) of the UEVLD gene. This alteration results from a C to T substitution at nucleotide position 1160, causing the serine (S) at amino acid position 387 to be replaced by a phenylalanine (F). 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

0.66

BayesDel_addAF

Uncertain

0.16

BayesDel_noAF

Pathogenic

0.19

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.31

T;.

Eigen

Pathogenic

0.86

Eigen_PC

Pathogenic

0.83

FATHMM_MKL

Uncertain

0.94

LIST_S2

Uncertain

0.93

D;D

M_CAP

Benign

0.062

MetaRNN

Pathogenic

0.88

D;D

MetaSVM

Uncertain

0.037

MutationAssessor

Pathogenic

3.1

M;.

MutationTaster

Benign

1.0

D;D;D;D;D;D

PrimateAI

Uncertain

0.57

PROVEAN

Pathogenic

-5.0

D;D

REVEL

Uncertain

0.52

Sift

Pathogenic

0.0

D;D

Sift4G

Uncertain

0.0020

D;D

Polyphen

1.0

D;.

Vest4

0.88

MVP

0.97

MPC

0.46

ClinPred

0.93

GERP RS

5.7

Varity_R

0.90

gMVP

0.82

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