chr12-10098874-C-A

Position:

• chr12-10098874-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_016511.4(CLEC1A):​c.49G>T​(p.Asp17Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: CLEC1A NM_016511.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.13

Genes affected

CLEC1A (HGNC:24355): (C-type lectin domain family 1 member A) 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 signaling, glycoprotein turnover, and roles in inflammation and immune response. The encoded protein may play a role in regulating dendritic cell function. This gene is closely linked to other CTL/CTLD superfamily members on chromosome 12p13 in the natural killer gene complex region. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2014]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.18650639).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CLEC1A	NM_016511.4	c.49G>T	p.Asp17Tyr	missense_variant	1/6	ENST00000315330.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CLEC1A	ENST00000315330.8	c.49G>T	p.Asp17Tyr	missense_variant	1/6	1	NM_016511.4	P1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 09, 2023

The c.49G>T (p.D17Y) alteration is located in exon 1 (coding exon 1) of the CLEC1A gene. This alteration results from a G to T substitution at nucleotide position 49, causing the aspartic acid (D) at amino acid position 17 to be replaced by a tyrosine (Y). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.093
BayesDel_addAF	Benign	-0.096	T
BayesDel_noAF	Benign	-0.38
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0025	T;.;.;.
Eigen	Benign	-0.031
Eigen_PC	Benign	0.054
FATHMM_MKL	Benign	0.46	N
LIST_S2	Benign	0.86	D;D;D;T
M_CAP	Benign	0.0044	T
MetaRNN	Benign	0.19	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.56	N;.;.;.
MutationTaster	Benign	0.85	N;N;N
PrimateAI	Benign	0.37	T
PROVEAN	Benign	3.1	N;N;N;N
REVEL	Benign	0.13
Sift	Benign	0.13	T;T;T;D
Sift4G	Benign	0.18	T;D;D;.
Polyphen		0.92	P;P;P;.
Vest4		0.59
MutPred		0.40		Gain of phosphorylation at D17 (P = 6e-04);Gain of phosphorylation at D17 (P = 6e-04);Gain of phosphorylation at D17 (P = 6e-04);Gain of phosphorylation at D17 (P = 6e-04);
MVP		0.67
MPC		0.27
ClinPred		0.82	D
GERP RS		4.6
Varity_R		0.082
gMVP		0.49

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr12-10251473;