19-50724595-T-G

Position:

• chr19-50724595-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_002975.3(CLEC11A):​c.520T>G​(p.Leu174Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000239 in 1,257,592 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 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: 0.0000024 (0 hom.)
• Consequence: CLEC11A NM_002975.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.595

Genes affected

CLEC11A (HGNC:10576): (C-type lectin domain containing 11A) This gene encodes a member of the C-type lectin superfamily. The encoded protein is a secreted sulfated glycoprotein and functions as a growth factor for primitive hematopoietic progenitor cells. An alternative splice variant has been described but its biological nature has not been determined. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.166652).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CLEC11A	NM_002975.3	c.520T>G	p.Leu174Val	missense_variant	3/4	ENST00000250340.9	NP_002966.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CLEC11A	ENST00000250340.9	c.520T>G	p.Leu174Val	missense_variant	3/4	1	NM_002975.3	ENSP00000250340.3
CLEC11A	ENST00000599973.1	c.520T>G	p.Leu174Val	missense_variant	3/4	1		ENSP00000471075.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000239 AC: 3 AN: 1257592 Hom.: 0 Cov.: 32 AF XY: 0.00000328 AC XY: 2 AN XY: 610670

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: 0.00000295

Gnomad4 OTH exome AF: 0.00

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

May 04, 2022

The c.520T>G (p.L174V) alteration is located in exon 3 (coding exon 3) of the CLEC11A gene. This alteration results from a T to G substitution at nucleotide position 520, causing the leucine (L) at amino acid position 174 to be replaced by a valine (V). 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	0.18
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	19
DANN	Benign	0.96
DEOGEN2	Benign	0.095	T;T;T
Eigen	Benign	-0.51
Eigen_PC	Benign	-0.54
FATHMM_MKL	Benign	0.45	N
LIST_S2	Benign	0.77	T;T;T
M_CAP	Uncertain	0.17	D
MetaRNN	Benign	0.17	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.8	L;.;.
PrimateAI	Pathogenic	0.85	D
PROVEAN	Benign	-1.3	N;.;.
REVEL	Benign	0.065
Sift	Benign	0.080	T;.;.
Sift4G	Uncertain	0.046	D;T;D
Polyphen		0.77	P;.;.
Vest4		0.16
MutPred		0.17		Gain of MoRF binding (P = 0.0819);Gain of MoRF binding (P = 0.0819);Gain of MoRF binding (P = 0.0819);
MVP		0.67
MPC		0.91
ClinPred		0.83	D
GERP RS		-1.8
Varity_R		0.093
gMVP		0.50

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-51227852;