19-50725124-G-C

Variant names:

• chr19-50725124-G-C
• rs761771291
• NM_002975.3:c.629G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_002975.3(CLEC11A):​c.629G>C​(p.Ser210Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000719 in 1,391,176 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/16 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S210I) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: CLEC11A NM_002975.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.03
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.048556417).

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.629G>C	p.Ser210Thr	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.629G>C	p.Ser210Thr	missense	Exon 4 of 4	ENSP00000250340.3	Q9Y240
	CLEC11A	ENST00000599973.1	TSL:1	c.678G>C	p.Glu226Asp	missense	Exon 4 of 4	ENSP00000471075.1	M0R081
	CLEC11A	ENST00000883282.1		c.620G>C	p.Ser207Thr	missense	Exon 4 of 4	ENSP00000553341.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.19e-7 AC: 1 AN: 1391176 Hom.: 0 Cov.: 47 AF XY: 0.00000146 AC XY: 1 AN XY: 686190

African (AFR) AF: 0.00 AC: 0 AN: 31136

American (AMR) AF: 0.00 AC: 0 AN: 35442

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24758

East Asian (EAS) AF: 0.00 AC: 0 AN: 35546

South Asian (SAS) AF: 0.00 AC: 0 AN: 78676

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 44778

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5612

European-Non Finnish (NFE) AF: 9.28e-7 AC: 1 AN: 1077526

Other (OTH) AF: 0.00 AC: 0 AN: 57702

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.026	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	15
DANN	Benign	0.54
DEOGEN2	Benign	0.022	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.2
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.23	T
M_CAP	Benign	0.064	D
MetaRNN	Benign	0.049	T
PhyloP100		1.0
Vest4		0.13
MVP		0.32
ClinPred		0.072	T
GERP RS		0.61
Varity_R		0.049
Mutation Taster		=88/12	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: rs761771291; hg19: chr19-51228381;