19-50725078-G-A

Position:

• chr19-50725078-G-A

Variant summary

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

The NM_002975.3(CLEC11A):​c.583G>A​(p.Glu195Lys) 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: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CLEC11A NM_002975.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.37

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=0.16222844).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CLEC11A	NM_002975.3	c.583G>A	p.Glu195Lys	missense_variant	4/4	ENST00000250340.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CLEC11A	ENST00000250340.9	c.583G>A	p.Glu195Lys	missense_variant	4/4	1	NM_002975.3	P1
CLEC11A	ENST00000599973.1	c.632G>A	p.Arg211Gln	missense_variant	4/4	1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1369478 Hom.: 0 Cov.: 48 AF XY: 0.00 AC XY: 0 AN XY: 674650

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

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

Dec 05, 2022

The c.583G>A (p.E195K) alteration is located in exon 4 (coding exon 4) of the CLEC11A gene. This alteration results from a G to A substitution at nucleotide position 583, causing the glutamic acid (E) at amino acid position 195 to be replaced by a lysine (K). 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	Pathogenic	0.63
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
CADD	Pathogenic	29
DANN	Uncertain	0.98
DEOGEN2	Benign	0.052	T;T
Eigen	Benign	-0.23
Eigen_PC	Benign	-0.25
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.84	T;T
M_CAP	Uncertain	0.11	D
MetaRNN	Benign	0.16	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.11	N;.
MutationTaster	Benign	0.91	D
PrimateAI	Pathogenic	0.92	D
PROVEAN	Benign	0.93	N;.
REVEL	Benign	0.18
Sift	Benign	0.90	T;.
Sift4G	Uncertain	0.013	D;D
Polyphen		0.99	D;.
Vest4		0.16
MutPred		0.56		Gain of MoRF binding (P = 0.0013);Gain of MoRF binding (P = 0.0013);
MVP		0.55
MPC		0.90
ClinPred		0.91	D
GERP RS		1.8
Varity_R		0.12
gMVP		0.66

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr19-51228335; COSMIC: COSV51573953;