rs2072663

Variant names:

• chr16-78030836-C-A
• rs2072663
• NM_005752.6:c.589C>A

Your query was ambiguous. Multiple possible variants found:

• chr16-78030836-C-A
• chr16-78030836-C-G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005752.6(CLEC3A):​c.589C>A​(p.Gln197Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.13 in 1,608,442 control chromosomes in the GnomAD database, including 14,311 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/17 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.12 (1219 hom., cov: 31)
  • Exomes 𝑓: 0.13 (13092 hom.)
• Consequence: CLEC3A NM_005752.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.14
• Publications: 18 publications found

Genes affected

CLEC3A (HGNC:2052): (C-type lectin domain family 3 member A) Predicted to enable carbohydrate binding activity. Predicted to be involved in ossification. Predicted to be active in extracellular space. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000261540 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0036537647).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.247 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005752.6. 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
	CLEC3A	NM_005752.6	MANE Select	c.589C>A	p.Gln197Lys	missense	Exon 3 of 3	NP_005743.5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLEC3A	ENST00000299642.10	TSL:1 MANE Select	c.589C>A	p.Gln197Lys	missense	Exon 3 of 3	ENSP00000299642.5
	ENSG00000261540	ENST00000563114.1	TSL:1	n.42-15707G>T		intron	N/A
	CLEC3A	ENST00000567430.2	TSL:1	n.115+8095C>A		intron	N/A	ENSP00000457211.2

Frequencies

GnomAD3 genomes AF: 0.119 AC: 18111 AN: 152028 Hom.: 1218 Cov.: 31

Gnomad AFR AF: 0.0834

Gnomad AMI AF: 0.0351

Gnomad AMR AF: 0.134

Gnomad ASJ AF: 0.162

Gnomad EAS AF: 0.258

Gnomad SAS AF: 0.102

Gnomad FIN AF: 0.0984

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.130

Gnomad OTH AF: 0.116

GnomAD2 exomes AF: 0.134 AC: 32955 AN: 246478 AF XY: 0.132

Gnomad AFR exome AF: 0.0832

Gnomad AMR exome AF: 0.137

Gnomad ASJ exome AF: 0.167

Gnomad EAS exome AF: 0.243

Gnomad FIN exome AF: 0.102

Gnomad NFE exome AF: 0.133

Gnomad OTH exome AF: 0.143

GnomAD4 exome AF: 0.131 AC: 191177 AN: 1456296 Hom.: 13092 Cov.: 33 AF XY: 0.131 AC XY: 94736 AN XY: 723720

African (AFR) AF: 0.0818 AC: 2729 AN: 33354

American (AMR) AF: 0.138 AC: 6123 AN: 44220

Ashkenazi Jewish (ASJ) AF: 0.165 AC: 4262 AN: 25802

East Asian (EAS) AF: 0.220 AC: 8719 AN: 39610

South Asian (SAS) AF: 0.101 AC: 8652 AN: 85488

European-Finnish (FIN) AF: 0.104 AC: 5532 AN: 53288

Middle Eastern (MID) AF: 0.114 AC: 642 AN: 5626

European-Non Finnish (NFE) AF: 0.132 AC: 146706 AN: 1108798

Other (OTH) AF: 0.130 AC: 7812 AN: 60110

GnomAD4 genome AF: 0.119 AC: 18129 AN: 152146 Hom.: 1219 Cov.: 31 AF XY: 0.119 AC XY: 8837 AN XY: 74382

African (AFR) AF: 0.0835 AC: 3466 AN: 41508

American (AMR) AF: 0.134 AC: 2048 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.162 AC: 563 AN: 3468

East Asian (EAS) AF: 0.258 AC: 1332 AN: 5154

South Asian (SAS) AF: 0.102 AC: 492 AN: 4816

European-Finnish (FIN) AF: 0.0984 AC: 1042 AN: 10592

Middle Eastern (MID) AF: 0.129 AC: 38 AN: 294

European-Non Finnish (NFE) AF: 0.130 AC: 8870 AN: 68000

Other (OTH) AF: 0.116 AC: 246 AN: 2114

Alfa AF: 0.129 Hom.: 6530

Bravo AF: 0.121

TwinsUK AF: 0.136 AC: 504

ALSPAC AF: 0.135 AC: 519

ESP6500AA AF: 0.0826 AC: 363

ESP6500EA AF: 0.133 AC: 1147

ExAC AF: 0.131 AC: 15863

Asia WGS AF: 0.154 AC: 536 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.092
BayesDel_addAF	Benign	-0.75	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	6.5
DANN	Benign	0.84
Eigen	Benign	-0.82
Eigen_PC	Benign	-0.68
FATHMM_MKL	Uncertain	0.80	D
LIST_S2	Benign	0.36	T
MetaRNN	Benign	0.0037	T
MetaSVM	Benign	-1.0	T
PhyloP100		3.1
PrimateAI	Benign	0.36	T
REVEL	Benign	0.098
Sift4G	Pathogenic	0.0	D
Vest4		0.051
MPC		0.0013
ClinPred		0.0022	T
GERP RS		3.9
Mutation Taster		=96/4	polymorphism (auto)

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: rs2072663; hg19: chr16-78064733; COSMIC: COSV55220029;