chr11-18566388-C-G

Position:

• chr11-18566388-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001040697.4(UEVLD):​c.452G>C​(p.Arg151Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: UEVLD NM_001040697.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.456

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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UEVLD	NM_001040697.4	c.452G>C	p.Arg151Pro	missense_variant	5/12	ENST00000396197.8	NP_001035787.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UEVLD	ENST00000396197.8	c.452G>C	p.Arg151Pro	missense_variant	5/12	5	NM_001040697.4	ENSP00000379500	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 30, 2022

The c.452G>C (p.R151P) alteration is located in exon 5 (coding exon 5) of the UEVLD gene. This alteration results from a G to C substitution at nucleotide position 452, causing the arginine (R) at amino acid position 151 to be replaced by a proline (P). 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	Uncertain	0.38
BayesDel_addAF	Benign	-0.0083	T
BayesDel_noAF	Benign	-0.25
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.062	T;.;.;.;.;.
Eigen	Benign	-0.23
Eigen_PC	Benign	-0.21
FATHMM_MKL	Benign	0.72	D
LIST_S2	Uncertain	0.92	D;D;D;D;D;D
M_CAP	Uncertain	0.16	D
MetaRNN	Benign	0.40	T;T;T;T;T;T
MetaSVM	Uncertain	-0.25	T
MutationAssessor	Benign	1.9	L;L;.;.;.;L
MutationTaster	Benign	1.0	D;N;N;N;N;N;N
PrimateAI	Benign	0.23	T
PROVEAN	Benign	-1.3	N;N;N;N;N;N
REVEL	Benign	0.24
Sift	Uncertain	0.0060	D;D;D;D;D;D
Sift4G	Uncertain	0.029	D;D;D;D;D;D
Polyphen		0.93	P;B;.;P;.;P
Vest4		0.50
MutPred		0.40		Gain of loop (P = 0.0435);Gain of loop (P = 0.0435);.;.;.;Gain of loop (P = 0.0435);
MVP		0.88
MPC		0.35
ClinPred		0.85	D
GERP RS		0.29
Varity_R		0.39
gMVP		0.36

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.25		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.25		Position offset: -4

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-18587935;