11-18534428-C-T

Variant names:

• chr11-18534428-C-T
• rs775586236
• NM_001040697.4:c.1150G>A

Variant summary

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

The NM_001040697.4(UEVLD):​c.1150G>A​(p.Gly384Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000703 in 1,422,386 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G384C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: UEVLD NM_001040697.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.64
• 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.1150G>A	p.Gly384Ser	missense	Exon 11 of 12	NP_001035787.1	Q8IX04-1
	UEVLD	NM_001261382.3		c.1084G>A	p.Gly362Ser	missense	Exon 10 of 11	NP_001248311.1	Q8IX04-6
	UEVLD	NM_001261384.3		c.760G>A	p.Gly254Ser	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.1150G>A	p.Gly384Ser	missense	Exon 11 of 12	ENSP00000379500.2	Q8IX04-1
	UEVLD	ENST00000543987.5	TSL:1	c.1125-1941G>A		intron	N/A	ENSP00000442974.1	Q8IX04-2
	UEVLD	ENST00000320750.10	TSL:1	c.1059-1941G>A		intron	N/A	ENSP00000323353.6	Q8IX04-3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.03e-7 AC: 1 AN: 1422386 Hom.: 0 Cov.: 30 AF XY: 0.00000142 AC XY: 1 AN XY: 706670

African (AFR) AF: 0.00 AC: 0 AN: 30940

American (AMR) AF: 0.00 AC: 0 AN: 34440

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25276

East Asian (EAS) AF: 0.00 AC: 0 AN: 36556

South Asian (SAS) AF: 0.00 AC: 0 AN: 77388

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53044

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5706

European-Non Finnish (NFE) AF: 9.09e-7 AC: 1 AN: 1100160

Other (OTH) AF: 0.00 AC: 0 AN: 58876

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.0029	T
BayesDel_noAF	Benign	-0.24
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.50	D
Eigen	Benign	0.014
Eigen_PC	Benign	-0.093
FATHMM_MKL	Uncertain	0.76	D
LIST_S2	Benign	0.79	T
M_CAP	Benign	0.056	D
MetaRNN	Uncertain	0.52	D
MetaSVM	Uncertain	0.020	D
MutationAssessor	Pathogenic	3.4	M
PhyloP100		1.6
PrimateAI	Benign	0.37	T
PROVEAN	Pathogenic	-5.2	D
REVEL	Uncertain	0.58
Sift	Uncertain	0.028	D
Sift4G	Uncertain	0.0060	D
Polyphen		1.0	D
Vest4		0.29
MutPred		0.76		Gain of relative solvent accessibility (P = 0.0275)
MVP		0.79
MPC		0.15
ClinPred		1.0	D
GERP RS		2.8
Varity_R		0.65
gMVP		0.85
Mutation Taster		=70/30	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs775586236; hg19: chr11-18555975; COSMIC: COSV57874698; COSMIC: COSV57874698;