rs2072663

Positions:

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

Variant summary

Our verdict is Benign. Variant got -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. 12/16 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 nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• 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

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CLEC3A	NM_005752.6	c.589C>A	p.Gln197Lys	missense_variant	3/3	ENST00000299642.10	NP_005743.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CLEC3A	ENST00000299642.10	c.589C>A	p.Gln197Lys	missense_variant	3/3	1	NM_005752.6	ENSP00000299642	P1
	ENST00000563114.1	n.42-15707G>T		intron_variant, non_coding_transcript_variant		1

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

GnomAD3 exomes AF: 0.134 AC: 32955 AN: 246478 Hom.: 2396 AF XY: 0.132 AC XY: 17541 AN XY: 133278

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 SAS exome AF: 0.103

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

Gnomad4 AFR exome AF: 0.0818

Gnomad4 AMR exome AF: 0.138

Gnomad4 ASJ exome AF: 0.165

Gnomad4 EAS exome AF: 0.220

Gnomad4 SAS exome AF: 0.101

Gnomad4 FIN exome AF: 0.104

Gnomad4 NFE exome AF: 0.132

Gnomad4 OTH exome AF: 0.130

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

Gnomad4 AFR AF: 0.0835

Gnomad4 AMR AF: 0.134

Gnomad4 ASJ AF: 0.162

Gnomad4 EAS AF: 0.258

Gnomad4 SAS AF: 0.102

Gnomad4 FIN AF: 0.0984

Gnomad4 NFE AF: 0.130

Gnomad4 OTH AF: 0.116

Alfa AF: 0.131 Hom.: 3507

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 v4.3

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
MutationTaster	Benign	1.0	P;P
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

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

Publications

LitVar

Other links and lift over

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