17-7076012-A-G

Position:

• chr17-7076012-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_001330070.2(CLEC10A):​c.412T>C​(p.Cys138Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00112 in 1,614,214 control chromosomes in the GnomAD database, including 14 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0051 (6 hom., cov: 31)
  • Exomes 𝑓: 0.00071 (8 hom.)
• Consequence: CLEC10A NM_001330070.2 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 2.67

Genes affected

CLEC10A (HGNC:16916): (C-type lectin domain containing 10A) This gene encodes a member of the C-type lectin/C-type lectin-like domain (CTL/CTLD) superfamily. Members of this family share a common protein fold and have diverse functions, such as cell adhesion, cell-cell signalling, glycoprotein turnover, and roles in inflammation and immune response. The encoded type 2 transmembrane protein may function as a cell surface antigen. Two transcript variants encoding distinct isoforms have been identified for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.01281932).
• BP6: Variant 17-7076012-A-G is Benign according to our data. Variant chr17-7076012-A-G is described in ClinVar as [Benign]. Clinvar id is 711652.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00507 (773/152328) while in subpopulation AFR AF= 0.017 (705/41576). AF 95% confidence interval is 0.0159. There are 6 homozygotes in gnomad4. There are 378 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CLEC10A	NM_001330070.2	c.412T>C	p.Cys138Arg	missense_variant	6/9	ENST00000416562.7	NP_001316999.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CLEC10A	ENST00000416562.7	c.412T>C	p.Cys138Arg	missense_variant	6/9	5	NM_001330070.2	ENSP00000414938	A2

Frequencies

GnomAD3 genomes AF: 0.00501 AC: 762 AN: 152210 Hom.: 6 Cov.: 31

Gnomad AFR AF: 0.0167

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00222

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.000376

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000235

Gnomad OTH AF: 0.00479

GnomAD3 exomes AF: 0.00146 AC: 366 AN: 251464 Hom.: 2 AF XY: 0.00107 AC XY: 145 AN XY: 135900

Gnomad AFR exome AF: 0.0169

Gnomad AMR exome AF: 0.00110

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000327

Gnomad FIN exome AF: 0.0000924

Gnomad NFE exome AF: 0.000369

Gnomad OTH exome AF: 0.00130

GnomAD4 exome AF: 0.000713 AC: 1042 AN: 1461886 Hom.: 8 Cov.: 35 AF XY: 0.000627 AC XY: 456 AN XY: 727246

Gnomad4 AFR exome AF: 0.0178

Gnomad4 AMR exome AF: 0.00134

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000580

Gnomad4 FIN exome AF: 0.000131

Gnomad4 NFE exome AF: 0.000233

Gnomad4 OTH exome AF: 0.00174

GnomAD4 genome AF: 0.00507 AC: 773 AN: 152328 Hom.: 6 Cov.: 31 AF XY: 0.00507 AC XY: 378 AN XY: 74490

Gnomad4 AFR AF: 0.0170

Gnomad4 AMR AF: 0.00222

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000414

Gnomad4 FIN AF: 0.000376

Gnomad4 NFE AF: 0.000235

Gnomad4 OTH AF: 0.00474

Alfa AF: 0.00132 Hom.: 1

Bravo AF: 0.00608

ESP6500AA AF: 0.0161 AC: 71

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.00158 AC: 192

Asia WGS AF: 0.00144 AC: 5 AN: 3478

EpiCase AF: 0.000327

EpiControl AF: 0.000178

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jun 21, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.61
BayesDel_addAF	Benign	-0.40	T
BayesDel_noAF	Benign	-0.33
CADD	Benign	18
DANN	Uncertain	0.98
DEOGEN2	Benign	0.10	T;.;.;.
Eigen	Benign	0.10
Eigen_PC	Benign	-0.11
FATHMM_MKL	Benign	0.33	N
LIST_S2	Benign	0.65	T;T;T;T
MetaRNN	Benign	0.013	T;T;T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Uncertain	2.6	M;.;.;.
MutationTaster	Benign	1.0	N;N;N;N
PrimateAI	Uncertain	0.54	T
PROVEAN	Pathogenic	-11	D;D;.;.
REVEL	Benign	0.19
Sift	Uncertain	0.0010	D;D;.;.
Sift4G	Uncertain	0.0050	D;D;D;D
Polyphen		1.0	D;.;D;D
Vest4		0.69
MVP		0.73
MPC		1.1
ClinPred		0.15	T
GERP RS		4.5
Varity_R		0.62
gMVP		0.66

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs112729653; hg19: chr17-6979331; COSMIC: COSV54702886; COSMIC: COSV54702886;