19-50724432-C-G

Variant names:

• chr19-50724432-C-G
• rs1248456268
• NM_002975.3:c.357C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_002975.3(CLEC11A):​c.357C>G​(p.Asp119Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000966 in 1,531,330 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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: 0.00010 (0 hom.)
• Consequence: CLEC11A NM_002975.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.511

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 -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.24422172).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CLEC11A	NM_002975.3	c.357C>G	p.Asp119Glu	missense_variant	Exon 3 of 4	ENST00000250340.9	NP_002966.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CLEC11A	ENST00000250340.9	c.357C>G	p.Asp119Glu	missense_variant	Exon 3 of 4	1	NM_002975.3	ENSP00000250340.3
CLEC11A	ENST00000599973.1	c.357C>G	p.Asp119Glu	missense_variant	Exon 3 of 4	1		ENSP00000471075.1

Frequencies

GnomAD3 genomes AF: 0.0000526 AC: 8 AN: 152110 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000118

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000560 AC: 10 AN: 178686 AF XY: 0.0000703

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000115

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000102 AC: 140 AN: 1379220 Hom.: 0 Cov.: 32 AF XY: 0.0000912 AC XY: 62 AN XY: 680050

Gnomad4 AFR exome AF: 0.00 AC: 0 AN: 30528

Gnomad4 AMR exome AF: 0.00 AC: 0 AN: 34682

Gnomad4 ASJ exome AF: 0.00 AC: 0 AN: 22458

Gnomad4 EAS exome AF: 0.00 AC: 0 AN: 36856

Gnomad4 SAS exome AF: 0.00 AC: 0 AN: 76468

Gnomad4 FIN exome AF: 0.00 AC: 0 AN: 39362

Gnomad4 NFE exome AF: 0.000129 AC: 139 AN: 1077926

Gnomad4 Remaining exome AF: 0.0000176 AC: 1 AN: 56872

GnomAD4 genome AF: 0.0000526 AC: 8 AN: 152110 Hom.: 0 Cov.: 32 AF XY: 0.0000673 AC XY: 5 AN XY: 74298

Gnomad4 AFR AF: 0.00 AC: 0 AN: 0

Gnomad4 AMR AF: 0.00 AC: 0 AN: 0

Gnomad4 ASJ AF: 0.00 AC: 0 AN: 0

Gnomad4 EAS AF: 0.00 AC: 0 AN: 0

Gnomad4 SAS AF: 0.00 AC: 0 AN: 0

Gnomad4 FIN AF: 0.00 AC: 0 AN: 0

Gnomad4 NFE AF: 0.000118 AC: 0.000117616 AN: 0.000117616

Gnomad4 OTH AF: 0.00 AC: 0 AN: 0

Alfa AF: 0.000142 Hom.: 0

Bravo AF: 0.0000453

ExAC AF: 0.0000337 AC: 4

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 18, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.357C>G (p.D119E) alteration is located in exon 3 (coding exon 3) of the CLEC11A gene. This alteration results from a C to G substitution at nucleotide position 357, causing the aspartic acid (D) at amino acid position 119 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	Uncertain	0.55
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	19
DANN	Uncertain	1.0
DEOGEN2	Benign	0.089	T;T;T
Eigen	Benign	-0.66
Eigen_PC	Benign	-0.55
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.71	T;T;T
M_CAP	Uncertain	0.16	D
MetaRNN	Benign	0.24	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.8	L;.;.
PrimateAI	Uncertain	0.77	T
PROVEAN	Benign	-0.94	N;.;.
REVEL	Benign	0.014
Sift	Benign	0.048	D;.;.
Sift4G	Pathogenic	0.0	D;D;D
Polyphen		0.0070	B;.;.
Vest4		0.38
MutPred		0.35		Gain of helix (P = 0.0425);Gain of helix (P = 0.0425);Gain of helix (P = 0.0425);
MVP		0.81
MPC		1.0
ClinPred		0.082	T
GERP RS		-0.26
Varity_R		0.083
gMVP		0.46
Mutation Taster		=92/8	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: rs1248456268; hg19: chr19-51227689;