Genetic Variant NM_001040697.4:c.938G>A (chr11-18544745-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001040697.4(UEVLD):c.938G>A(p.Arg313Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000172 in 1,568,736 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000016 ( 0 hom. )

Consequence

UEVLD
NM_001040697.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.118

Publications

3 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.19739786).

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.938G>A	p.Arg313Gln	missense	Exon 9 of 12	NP_001035787.1	Q8IX04-1
UEVLD	NM_001261382.3		c.872G>A	p.Arg291Gln	missense	Exon 8 of 11	NP_001248311.1	Q8IX04-6
UEVLD	NM_018314.6		c.938G>A	p.Arg313Gln	missense	Exon 9 of 11	NP_060784.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
UEVLD	ENST00000396197.8	TSL:5 MANE Select	c.938G>A	p.Arg313Gln	missense	Exon 9 of 12	ENSP00000379500.2	Q8IX04-1
UEVLD	ENST00000543987.5	TSL:1	c.938G>A	p.Arg313Gln	missense	Exon 9 of 11	ENSP00000442974.1	Q8IX04-2
UEVLD	ENST00000320750.10	TSL:1	c.872G>A	p.Arg291Gln	missense	Exon 8 of 10	ENSP00000323353.6	Q8IX04-3

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

151862

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000969

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:

0.0000675

AC:

AN:

207400

AF XY:

0.0000616

show subpopulations

Gnomad AFR exome

AF:

0.000153

Gnomad AMR exome

AF:

0.000436

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000757

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000162

AC:

AN:

1416874

Hom.:

Cov.:

AF XY:

0.0000156

AC XY:

AN XY:

704290

show subpopulations

African (AFR)

AF:

0.0000330

AC:

AN:

30330

American (AMR)

AF:

0.000352

AC:

AN:

34074

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25194

East Asian (EAS)

AF:

0.0000284

AC:

AN:

35222

South Asian (SAS)

AF:

0.0000511

AC:

AN:

78340

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53008

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5678

European-Non Finnish (NFE)

AF:

0.00000456

AC:

AN:

1096458

Other (OTH)

AF:

0.00

AC:

AN:

58570

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.458

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:

0.0000263

AC:

AN:

151862

Hom.:

Cov.:

AF XY:

0.0000405

AC XY:

AN XY:

74140

show subpopulations

African (AFR)

AF:

0.0000969

AC:

AN:

41294

American (AMR)

AF:

0.00

AC:

AN:

15220

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5200

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10536

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68004

Other (OTH)

AF:

0.00

AC:

AN:

2080

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

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:

0.0000494

Hom.:

Bravo

AF:

0.0000189

ESP6500AA

AF:

0.000455

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000494

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

0.071

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.29

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Uncertain

0.63

Eigen

Benign

-0.41

Eigen_PC

Benign

-0.31

FATHMM_MKL

Benign

0.65

LIST_S2

Uncertain

0.90

M_CAP

Benign

0.038

MetaRNN

Benign

0.20

MetaSVM

Uncertain

-0.14

MutationAssessor

Benign

1.4

PhyloP100

0.12

PrimateAI

Benign

0.20

PROVEAN

Benign

-2.1

REVEL

Benign

0.28

Sift

Benign

0.10

Sift4G

Benign

0.12

Polyphen

0.12

Vest4

0.29

MVP

0.95

MPC

0.12

ClinPred

0.030

GERP RS

1.4

Varity_R

0.31

gMVP

0.57

Mutation Taster

=80/20

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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