chr19-50724532-A-C

Variant names:

• chr19-50724532-A-C
• rs771589211
• NM_002975.3:c.457A>C

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_002975.3(CLEC11A):​c.457A>C​(p.Thr153Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000169 in 1,540,374 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 0.000020 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000017 (0 hom.)
• Consequence: CLEC11A NM_002975.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.27
• Publications: 1 publications found

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: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.40979266).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002975.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLEC11A	NM_002975.3	MANE Select	c.457A>C	p.Thr153Pro	missense	Exon 3 of 4	NP_002966.1	Q9Y240

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLEC11A	ENST00000250340.9	TSL:1 MANE Select	c.457A>C	p.Thr153Pro	missense	Exon 3 of 4	ENSP00000250340.3	Q9Y240
	CLEC11A	ENST00000599973.1	TSL:1	c.457A>C	p.Thr153Pro	missense	Exon 3 of 4	ENSP00000471075.1	M0R081
	CLEC11A	ENST00000883282.1		c.448A>C	p.Thr150Pro	missense	Exon 3 of 4	ENSP00000553341.1

Frequencies

GnomAD3 genomes AF: 0.0000197 AC: 3 AN: 152132 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

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: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000273 AC: 4 AN: 146648 AF XY: 0.0000368

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000394

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000479

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000166 AC: 23 AN: 1388242 Hom.: 0 Cov.: 32 AF XY: 0.0000190 AC XY: 13 AN XY: 685916

African (AFR) AF: 0.00 AC: 0 AN: 30874

American (AMR) AF: 0.0000268 AC: 1 AN: 37288

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24760

East Asian (EAS) AF: 0.00 AC: 0 AN: 35754

South Asian (SAS) AF: 0.00 AC: 0 AN: 79764

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 35226

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4422

European-Non Finnish (NFE) AF: 0.0000203 AC: 22 AN: 1082472

Other (OTH) AF: 0.00 AC: 0 AN: 57682

GnomAD4 genome AF: 0.0000197 AC: 3 AN: 152132 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74314

African (AFR) AF: 0.0000241 AC: 1 AN: 41436

American (AMR) AF: 0.0000654 AC: 1 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10614

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68010

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000227

ExAC AF: 0.0000178 AC: 2

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.27
BayesDel_addAF	Benign	-0.016	T
BayesDel_noAF	Benign	-0.12
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.11	T
Eigen	Uncertain	0.36
Eigen_PC	Uncertain	0.36
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.57	T
M_CAP	Uncertain	0.19	D
MetaRNN	Benign	0.41	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	1.8	L
PhyloP100		1.3
PrimateAI	Pathogenic	0.84	D
PROVEAN	Benign	-2.0	N
REVEL	Benign	0.20
Sift	Benign	0.040	D
Sift4G	Uncertain	0.042	D
Polyphen		1.0	D
Vest4		0.57
MutPred		0.37		Loss of phosphorylation at T153 (P = 0.0506)
MVP		0.87
MPC		1.2
ClinPred		0.41	T
GERP RS		4.5
Varity_R		0.61
gMVP		0.80
Mutation Taster		=79/21	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

Other links and lift over

dbSNP: rs771589211; hg19: chr19-51227789;