rs761875180

Variant names:

• chr11-18534448-A-G
• rs761875180
• NM_001040697.4:c.1130T>C

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001040697.4(UEVLD):​c.1130T>C​(p.Met377Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00000141 in 1,417,986 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: UEVLD NM_001040697.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.42
• Publications: 0 publications found

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]

ACMG classification

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

• PM2: Very rare variant in population databases, with high coverage

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UEVLD	NM_001040697.4	MANE Select	c.1130T>C	p.Met377Thr	missense	Exon 11 of 12	NP_001035787.1	Q8IX04-1
	UEVLD	NM_001261382.3		c.1064T>C	p.Met355Thr	missense	Exon 10 of 11	NP_001248311.1	Q8IX04-6
	UEVLD	NM_001261384.3		c.740T>C	p.Met247Thr	missense	Exon 9 of 10	NP_001248313.1	B4DIA9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UEVLD	ENST00000396197.8	TSL:5 MANE Select	c.1130T>C	p.Met377Thr	missense	Exon 11 of 12	ENSP00000379500.2	Q8IX04-1
	UEVLD	ENST00000543987.5	TSL:1	c.1124+1958T>C		intron	N/A	ENSP00000442974.1	Q8IX04-2
	UEVLD	ENST00000320750.10	TSL:1	c.1058+1958T>C		intron	N/A	ENSP00000323353.6	Q8IX04-3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000486 AC: 1 AN: 205698 AF XY: 0.00000885

Gnomad AFR exome AF: 0.0000748

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: 0.00000141 AC: 2 AN: 1417986 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 704400

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 30702

American (AMR) AF: 0.00 AC: 0 AN: 32768

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25026

East Asian (EAS) AF: 0.00 AC: 0 AN: 36604

South Asian (SAS) AF: 0.0000131 AC: 1 AN: 76372

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53018

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5680

European-Non Finnish (NFE) AF: 9.10e-7 AC: 1 AN: 1099030

Other (OTH) AF: 0.00 AC: 0 AN: 58786

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

ExAC AF: 0.00000828 AC: 1

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.20
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.098	T
Eigen	Uncertain	0.23
Eigen_PC	Uncertain	0.34
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.81	T
M_CAP	Uncertain	0.086	D
MetaRNN	Uncertain	0.58	D
MetaSVM	Benign	-0.64	T
MutationAssessor	Benign	1.7	L
PhyloP100		6.4
PrimateAI	Uncertain	0.53	T
PROVEAN	Benign	-1.7	N
REVEL	Benign	0.28
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.018	D
Polyphen		0.46	P
Vest4		0.58
MutPred		0.61		Loss of catalytic residue at M377 (P = 0.0221)
MVP		0.80
MPC		0.22
ClinPred		0.76	D
GERP RS		5.7
Varity_R		0.62
gMVP		0.70
Mutation Taster		=52/48	polymorphism

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

Other links and lift over

dbSNP: rs761875180; hg19: chr11-18555995; COSMIC: COSV57874117; COSMIC: COSV57874117;