chr17-7076919-C-T

Variant names:

• chr17-7076919-C-T
• rs199755396
• NM_001330070.2:c.253G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001330070.2(CLEC10A):​c.253G>A​(p.Ala85Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000397 in 1,613,874 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000026 (0 hom., cov: 28)
  • Exomes 𝑓: 0.000041 (0 hom.)
• Consequence: CLEC10A NM_001330070.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0690
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.11393851).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLEC10A	NM_001330070.2	MANE Select	c.253G>A	p.Ala85Thr	missense	Exon 4 of 9	NP_001316999.1	J3KR22
	CLEC10A	NM_182906.4		c.253G>A	p.Ala85Thr	missense	Exon 4 of 9	NP_878910.1	Q8IUN9-1
	CLEC10A	NM_006344.4		c.253G>A	p.Ala85Thr	missense	Exon 4 of 9	NP_006335.2	Q8IUN9-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLEC10A	ENST00000416562.7	TSL:5 MANE Select	c.253G>A	p.Ala85Thr	missense	Exon 4 of 9	ENSP00000414938.2	J3KR22
	CLEC10A	ENST00000254868.8	TSL:1	c.253G>A	p.Ala85Thr	missense	Exon 4 of 9	ENSP00000254868.4	Q8IUN9-1
	CLEC10A	ENST00000571664.1	TSL:1	c.253G>A	p.Ala85Thr	missense	Exon 4 of 9	ENSP00000460252.1	Q8IUN9-2

Frequencies

GnomAD3 genomes AF: 0.0000263 AC: 4 AN: 151994 Hom.: 0 Cov.: 28

Gnomad AFR AF: 0.0000242

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000835 AC: 21 AN: 251484 AF XY: 0.0000809

Gnomad AFR exome AF: 0.0000615

Gnomad AMR exome AF: 0.0000867

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000703

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000410 AC: 60 AN: 1461880 Hom.: 0 Cov.: 32 AF XY: 0.0000495 AC XY: 36 AN XY: 727246

African (AFR) AF: 0.0000299 AC: 1 AN: 33480

American (AMR) AF: 0.0000671 AC: 3 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.000406 AC: 35 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.000173 AC: 1 AN: 5766

European-Non Finnish (NFE) AF: 0.0000180 AC: 20 AN: 1112002

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome AF: 0.0000263 AC: 4 AN: 151994 Hom.: 0 Cov.: 28 AF XY: 0.0000135 AC XY: 1 AN XY: 74246

African (AFR) AF: 0.0000242 AC: 1 AN: 41356

American (AMR) AF: 0.00 AC: 0 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5194

South Asian (SAS) AF: 0.00 AC: 0 AN: 4814

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10614

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 67982

Other (OTH) AF: 0.00 AC: 0 AN: 2084

Alfa AF: 0.0000532 Hom.: 0

Bravo AF: 0.0000453

ExAC AF: 0.000107 AC: 13

EpiCase AF: 0.0000545

EpiControl AF: 0.000178

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.083
BayesDel_addAF	Benign	-0.43	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	4.7
DANN	Uncertain	1.0
DEOGEN2	Benign	0.015	T
Eigen	Benign	-0.22
Eigen_PC	Benign	-0.37
FATHMM_MKL	Benign	0.032	N
LIST_S2	Benign	0.47	T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.8	L
PhyloP100		-0.069
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.074
Sift	Benign	0.66	T
Sift4G	Benign	0.33	T
Polyphen		0.99	D
Vest4		0.066
MVP		0.46
MPC		0.33
ClinPred		0.13	T
GERP RS		1.5
PromoterAI		0.0051	Neutral
Varity_R		0.031
gMVP		0.13
Mutation Taster		=98/2	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: rs199755396; hg19: chr17-6980238;