chr19-50725144-C-T

Variant names:

• chr19-50725144-C-T
• rs746583975
• NM_002975.3:c.649C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_002975.3(CLEC11A):​c.649C>T​(p.Arg217Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000642 in 1,402,924 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: not found (cov: 33)
  • Exomes 𝑓: 0.0000064 (0 hom.)
• Consequence: CLEC11A NM_002975.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.222
• Publications: 0 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.23397544).

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.649C>T	p.Arg217Cys	missense	Exon 4 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.649C>T	p.Arg217Cys	missense	Exon 4 of 4	ENSP00000250340.3	Q9Y240
	CLEC11A	ENST00000599973.1	TSL:1	c.698C>T	p.Pro233Leu	missense	Exon 4 of 4	ENSP00000471075.1	M0R081
	CLEC11A	ENST00000883282.1		c.640C>T	p.Arg214Cys	missense	Exon 4 of 4	ENSP00000553341.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000664 AC: 1 AN: 150530 AF XY: 0.0000121

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: 0.0000174

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000642 AC: 9 AN: 1402924 Hom.: 0 Cov.: 48 AF XY: 0.00000866 AC XY: 6 AN XY: 692868

African (AFR) AF: 0.00 AC: 0 AN: 31594

American (AMR) AF: 0.00 AC: 0 AN: 36496

Ashkenazi Jewish (ASJ) AF: 0.0000399 AC: 1 AN: 25084

East Asian (EAS) AF: 0.00 AC: 0 AN: 36126

South Asian (SAS) AF: 0.0000125 AC: 1 AN: 79934

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 46250

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5652

European-Non Finnish (NFE) AF: 0.00000646 AC: 7 AN: 1083596

Other (OTH) AF: 0.00 AC: 0 AN: 58192

GnomAD4 genome Cov.: 33

Alfa AF: 0.0000285 Hom.: 0

ExAC AF: 0.00000890 AC: 1

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	Uncertain	0.51
BayesDel_addAF	Benign	-0.040	T
BayesDel_noAF	Benign	-0.41
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0056	T
Eigen	Benign	-0.31
Eigen_PC	Benign	-0.51
FATHMM_MKL	Benign	0.69	D
LIST_S2	Benign	0.35	T
M_CAP	Uncertain	0.24	D
MetaRNN	Benign	0.23	T
PhyloP100		0.22
Vest4		0.32
MVP		0.73
ClinPred		0.88	D
GERP RS		0.47
Varity_R		0.15
Mutation Taster		=76/24	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: rs746583975; hg19: chr19-51228401;