Genetic Variant UEVLD:p.Gly384Cys (chr11-18534428-C-A) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PP3_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

Publications

0 publications found

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 was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.917

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001040697.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
UEVLD	NM_001040697.4	MANE Select	c.1150G>T	p.Gly384Cys	missense	Exon 11 of 12	NP_001035787.1	Q8IX04-1
UEVLD	NM_001261382.3		c.1084G>T	p.Gly362Cys	missense	Exon 10 of 11	NP_001248311.1	Q8IX04-6
UEVLD	NM_001261384.3		c.760G>T	p.Gly254Cys	missense	Exon 9 of 10	NP_001248313.1	B4DIA9

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
UEVLD	ENST00000396197.8	TSL:5 MANE Select	c.1150G>T	p.Gly384Cys	missense	Exon 11 of 12	ENSP00000379500.2	Q8IX04-1
UEVLD	ENST00000543987.5	TSL:1	c.1125-1941G>T		intron	N/A	ENSP00000442974.1	Q8IX04-2
UEVLD	ENST00000320750.10	TSL:1	c.1059-1941G>T		intron	N/A	ENSP00000323353.6	Q8IX04-3

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

GnomAD2 exomes

AF:

0.0000332

AC:

AN:

210884

AF XY:

0.0000260

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 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

African (AFR)

AF:

0.000388

AC:

AN:

30940

American (AMR)

AF:

0.00

AC:

AN:

34440

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25276

East Asian (EAS)

AF:

0.00

AC:

AN:

36556

South Asian (SAS)

AF:

0.00

AC:

AN:

77388

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53044

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5706

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1100160

Other (OTH)

AF:

0.0000170

AC:

AN:

58876

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.471

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000105

AC:

AN:

152122

Hom.:

Cov.:

AF XY:

0.000135

AC XY:

AN XY:

74320

show subpopulations

African (AFR)

AF:

0.000386

AC:

AN:

41408

American (AMR)

AF:

0.00

AC:

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5196

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10610

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68016

Other (OTH)

AF:

0.00

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000214

Hom.:

Bravo

AF:

0.000136

ExAC

AF:

0.0000331

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.34

BayesDel_addAF

Benign

-0.098

BayesDel_noAF

Uncertain

-0.020

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.61

Eigen

Benign

0.054

Eigen_PC

Benign

-0.067

FATHMM_MKL

Uncertain

0.84

LIST_S2

Uncertain

0.89

M_CAP

Uncertain

0.23

MetaRNN

Pathogenic

0.92

MetaSVM

Uncertain

0.12

MutationAssessor

Pathogenic

3.4

PhyloP100

1.6

PrimateAI

Benign

0.39

PROVEAN

Pathogenic

-7.8

REVEL

Uncertain

0.64

Sift

Uncertain

0.011

Sift4G

Pathogenic

0.0010

Polyphen

1.0

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

Mutation Taster

=67/33

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over