19-50724569-G-C

Variant names:

• chr19-50724569-G-C
• rs752036565
• NM_002975.3:c.494G>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.494G>C​(p.Gly165Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000767 in 1,302,968 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 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. G165V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.7e-7 (0 hom.)
• Consequence: CLEC11A NM_002975.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.361
• 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=0.05081001).

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.494G>C	p.Gly165Ala	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.494G>C	p.Gly165Ala	missense	Exon 3 of 4	ENSP00000250340.3	Q9Y240
	CLEC11A	ENST00000599973.1	TSL:1	c.494G>C	p.Gly165Ala	missense	Exon 3 of 4	ENSP00000471075.1	M0R081
	CLEC11A	ENST00000883282.1		c.485G>C	p.Gly162Ala	missense	Exon 3 of 4	ENSP00000553341.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.67e-7 AC: 1 AN: 1302968 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 636698

African (AFR) AF: 0.00 AC: 0 AN: 26426

American (AMR) AF: 0.00 AC: 0 AN: 23334

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21080

East Asian (EAS) AF: 0.00 AC: 0 AN: 32000

South Asian (SAS) AF: 0.00 AC: 0 AN: 68198

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 32230

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4202

European-Non Finnish (NFE) AF: 9.60e-7 AC: 1 AN: 1041356

Other (OTH) AF: 0.00 AC: 0 AN: 54142

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.072
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.73
CADD	Benign	17
DANN	Benign	0.80
DEOGEN2	Benign	0.065	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.40	N
LIST_S2	Benign	0.50	T
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.051	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.69	N
PhyloP100		0.36
PrimateAI	Uncertain	0.73	T
PROVEAN	Benign	0.64	N
REVEL	Benign	0.059
Sift	Benign	0.67	T
Sift4G	Benign	0.60	T
Polyphen		0.0030	B
Vest4		0.16
MutPred		0.25		Gain of helix (P = 0.0199)
MVP		0.51
MPC		0.41
ClinPred		0.047	T
GERP RS		-3.6
Varity_R		0.039
gMVP		0.23
Mutation Taster		=99/1	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: rs752036565; hg19: chr19-51227826;