chr17-7078078-A-G

Variant names:

• chr17-7078078-A-G
• rs90951
• NM_001330070.2:c.103T>C

Variant summary

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

The NM_001330070.2(CLEC10A):​c.103T>C​(p.Cys35Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.369 in 1,611,730 control chromosomes in the GnomAD database, including 121,453 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 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 0.49 (22035 hom., cov: 31)
  • Exomes 𝑓: 0.36 (99418 hom.)
• Consequence: CLEC10A NM_001330070.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0250
• Publications: 32 publications found

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

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

• BP4: Computational evidence support a benign effect (MetaRNN=1.672348E-6).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.824 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001330070.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLEC10A	NM_001330070.2	MANE Select	c.103T>C	p.Cys35Arg	missense	Exon 3 of 9	NP_001316999.1
	CLEC10A	NM_182906.4		c.103T>C	p.Cys35Arg	missense	Exon 3 of 9	NP_878910.1
	CLEC10A	NM_006344.4		c.103T>C	p.Cys35Arg	missense	Exon 3 of 9	NP_006335.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLEC10A	ENST00000416562.7	TSL:5 MANE Select	c.103T>C	p.Cys35Arg	missense	Exon 3 of 9	ENSP00000414938.2
	CLEC10A	ENST00000254868.8	TSL:1	c.103T>C	p.Cys35Arg	missense	Exon 3 of 9	ENSP00000254868.4
	CLEC10A	ENST00000571664.1	TSL:1	c.103T>C	p.Cys35Arg	missense	Exon 3 of 9	ENSP00000460252.1

Frequencies

GnomAD3 genomes AF: 0.492 AC: 74817 AN: 151944 Hom.: 21982 Cov.: 31

Gnomad AFR AF: 0.831

Gnomad AMI AF: 0.379

Gnomad AMR AF: 0.384

Gnomad ASJ AF: 0.507

Gnomad EAS AF: 0.466

Gnomad SAS AF: 0.300

Gnomad FIN AF: 0.392

Gnomad MID AF: 0.503

Gnomad NFE AF: 0.343

Gnomad OTH AF: 0.476

GnomAD2 exomes AF: 0.387 AC: 97253 AN: 251058 AF XY: 0.380

Gnomad AFR exome AF: 0.844

Gnomad AMR exome AF: 0.282

Gnomad ASJ exome AF: 0.518

Gnomad EAS exome AF: 0.483

Gnomad FIN exome AF: 0.397

Gnomad NFE exome AF: 0.348

Gnomad OTH exome AF: 0.397

GnomAD4 exome AF: 0.357 AC: 520596 AN: 1459668 Hom.: 99418 Cov.: 35 AF XY: 0.356 AC XY: 258673 AN XY: 726202

African (AFR) AF: 0.854 AC: 28559 AN: 33442

American (AMR) AF: 0.295 AC: 13172 AN: 44708

Ashkenazi Jewish (ASJ) AF: 0.515 AC: 13453 AN: 26100

East Asian (EAS) AF: 0.476 AC: 18906 AN: 39678

South Asian (SAS) AF: 0.308 AC: 26558 AN: 86174

European-Finnish (FIN) AF: 0.391 AC: 20857 AN: 53322

Middle Eastern (MID) AF: 0.502 AC: 2889 AN: 5760

European-Non Finnish (NFE) AF: 0.336 AC: 372536 AN: 1110160

Other (OTH) AF: 0.392 AC: 23666 AN: 60324

GnomAD4 genome AF: 0.493 AC: 74917 AN: 152062 Hom.: 22035 Cov.: 31 AF XY: 0.491 AC XY: 36452 AN XY: 74314

African (AFR) AF: 0.831 AC: 34505 AN: 41500

American (AMR) AF: 0.384 AC: 5853 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.507 AC: 1761 AN: 3472

East Asian (EAS) AF: 0.466 AC: 2402 AN: 5160

South Asian (SAS) AF: 0.300 AC: 1445 AN: 4820

European-Finnish (FIN) AF: 0.392 AC: 4138 AN: 10568

Middle Eastern (MID) AF: 0.507 AC: 149 AN: 294

European-Non Finnish (NFE) AF: 0.343 AC: 23317 AN: 67972

Other (OTH) AF: 0.475 AC: 1002 AN: 2108

Alfa AF: 0.401 Hom.: 49503

Bravo AF: 0.514

TwinsUK AF: 0.344 AC: 1277

ALSPAC AF: 0.330 AC: 1270

ESP6500AA AF: 0.819 AC: 3608

ESP6500EA AF: 0.355 AC: 3053

ExAC AF: 0.394 AC: 47850

Asia WGS AF: 0.402 AC: 1398 AN: 3478

EpiCase AF: 0.373

EpiControl AF: 0.370

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.061
BayesDel_addAF	Benign	-0.82	T
BayesDel_noAF	Benign	-0.81
CADD	Benign	11
DANN	Benign	0.46
DEOGEN2	Benign	0.038	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.014	N
LIST_S2	Benign	0.13	T
MetaRNN	Benign	0.0000017	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.80	N
PhyloP100		-0.025
PrimateAI	Benign	0.18	T
PROVEAN	Pathogenic	-4.9	D
REVEL	Benign	0.042
Sift	Benign	0.13	T
Sift4G	Benign	0.18	T
Polyphen		0.0	B
Vest4		0.027
MPC		0.43
ClinPred		0.0085	T
GERP RS		-0.38
Varity_R		0.26
gMVP		0.20
Mutation Taster		=100/0	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: rs90951; hg19: chr17-6981397; COSMIC: COSV54701296; COSMIC: COSV54701296;