11-18532334-G-C

Variant names:

• chr11-18532334-G-C
• rs1009171786
• NM_001040697.4:c.1402C>G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001040697.4(UEVLD):​c.1402C>G​(p.Gln468Glu) variant causes a missense change. The variant allele was found at a frequency of 0.0000186 in 1,452,430 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000019 (0 hom.)
• Consequence: UEVLD NM_001040697.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.36

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.32692015).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UEVLD	NM_001040697.4	c.1402C>G	p.Gln468Glu	missense_variant	Exon 12 of 12	ENST00000396197.8	NP_001035787.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UEVLD	ENST00000396197.8	c.1402C>G	p.Gln468Glu	missense_variant	Exon 12 of 12	5	NM_001040697.4	ENSP00000379500.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.0000186 AC: 27 AN: 1452430 Hom.: 0 Cov.: 30 AF XY: 0.0000208 AC XY: 15 AN XY: 722276

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000234

Gnomad4 OTH exome AF: 0.0000167

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000565 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Sep 20, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1402C>G (p.Q468E) alteration is located in exon 12 (coding exon 12) of the UEVLD gene. This alteration results from a C to G substitution at nucleotide position 1402, causing the glutamine (Q) at amino acid position 468 to be replaced by a glutamic acid (E). 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	Benign	0.093
BayesDel_addAF	Benign	-0.027	T
BayesDel_noAF	Benign	-0.28
CADD	Uncertain	24
DANN	Benign	0.94
DEOGEN2	Benign	0.031	T;.
Eigen	Uncertain	0.25
Eigen_PC	Uncertain	0.29
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.82	T;T
M_CAP	Benign	0.028	D
MetaRNN	Benign	0.33	T;T
MetaSVM	Benign	-0.87	T
MutationAssessor	Benign	1.0	L;.
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	-0.040	N;N
REVEL	Benign	0.10
Sift	Benign	0.44	T;T
Sift4G	Benign	0.41	T;T
Polyphen		0.92	P;.
Vest4		0.50
MVP		0.71
MPC		0.48
ClinPred		0.86	D
GERP RS		4.4
Varity_R		0.58
gMVP		0.75

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

LitVar

Other links and lift over

dbSNP: rs1009171786; hg19: chr11-18553881;