19-50723647-G-A

Variant names:

• chr19-50723647-G-A
• rs753355501
• NM_002975.3:c.122G>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_002975.3(CLEC11A):​c.122G>A​(p.Arg41Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000946 in 1,595,820 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/23 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000053 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000099 (0 hom.)
• Consequence: CLEC11A NM_002975.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.136

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

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0440737).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CLEC11A	NM_002975.3	c.122G>A	p.Arg41Gln	missense_variant	Exon 1 of 4	ENST00000250340.9	NP_002966.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CLEC11A	ENST00000250340.9	c.122G>A	p.Arg41Gln	missense_variant	Exon 1 of 4	1	NM_002975.3	ENSP00000250340.3
CLEC11A	ENST00000599973.1	c.122G>A	p.Arg41Gln	missense_variant	Exon 1 of 4	1		ENSP00000471075.1

Frequencies

GnomAD3 genomes AF: 0.0000526 AC: 8 AN: 152030 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000262

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000208

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000160 AC: 37 AN: 231582 AF XY: 0.0000644

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000704

Gnomad ASJ exome AF: 0.000121

Gnomad EAS exome AF: 0.000166

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000958

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000990 AC: 143 AN: 1443790 Hom.: 0 Cov.: 32 AF XY: 0.0000935 AC XY: 67 AN XY: 716758

Gnomad4 AFR exome AF: 0.0000303 AC: 1 AN: 33040

Gnomad4 AMR exome AF: 0.000698 AC: 30 AN: 42974

Gnomad4 ASJ exome AF: 0.00 AC: 0 AN: 24742

Gnomad4 EAS exome AF: 0.0000505 AC: 2 AN: 39588

Gnomad4 SAS exome AF: 0.00 AC: 0 AN: 82704

Gnomad4 FIN exome AF: 0.00 AC: 0 AN: 52518

Gnomad4 NFE exome AF: 0.0000960 AC: 106 AN: 1104442

Gnomad4 Remaining exome AF: 0.0000672 AC: 4 AN: 59548

GnomAD4 genome AF: 0.0000526 AC: 8 AN: 152030 Hom.: 0 Cov.: 32 AF XY: 0.0000539 AC XY: 4 AN XY: 74272

Gnomad4 AFR AF: 0.00 AC: 0 AN: 0

Gnomad4 AMR AF: 0.000262 AC: 0.000262055 AN: 0.000262055

Gnomad4 ASJ AF: 0.00 AC: 0 AN: 0

Gnomad4 EAS AF: 0.00 AC: 0 AN: 0

Gnomad4 SAS AF: 0.000208 AC: 0.000207555 AN: 0.000207555

Gnomad4 FIN AF: 0.00 AC: 0 AN: 0

Gnomad4 NFE AF: 0.0000441 AC: 0.0000441189 AN: 0.0000441189

Gnomad4 OTH AF: 0.00 AC: 0 AN: 0

Alfa AF: 0.0000501 Hom.: 0

Bravo AF: 0.0000718

ExAC AF: 0.0000741 AC: 9

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Nov 21, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.122G>A (p.R41Q) alteration is located in exon 1 (coding exon 1) of the CLEC11A gene. This alteration results from a G to A substitution at nucleotide position 122, causing the arginine (R) at amino acid position 41 to be replaced by a glutamine (Q). 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	0.077
BayesDel_addAF	Benign	-0.48	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	16
DANN	Uncertain	1.0
DEOGEN2	Benign	0.067	T;T;T
Eigen	Benign	-0.47
Eigen_PC	Benign	-0.39
FATHMM_MKL	Benign	0.18	N
LIST_S2	Benign	0.76	T;T;T
M_CAP	Benign	0.0073	T
MetaRNN	Benign	0.044	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.97	L;.;.
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-0.34	N;.;.
REVEL	Benign	0.062
Sift	Benign	0.17	T;.;.
Sift4G	Uncertain	0.043	D;D;D
Polyphen		0.026	B;.;.
Vest4		0.070
MVP		0.74
MPC		0.44
ClinPred		0.047	T
GERP RS		0.93
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.1
Varity_R		0.064
gMVP		0.097
Mutation Taster		=98/2	polymorphism

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: rs753355501; hg19: chr19-51226904; COSMIC: COSV51574348; COSMIC: COSV51574348;