NM_197947.3:c.714T>A

Variant names:

• chr12-10118488-A-T
• rs16910526
• NM_197947.3:c.714T>A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_197947.3(CLEC7A):​c.714T>A​(p.Tyr238*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CLEC7A NM_197947.3 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0690
• Publications: 3 publications found

Genes affected

CLEC7A (HGNC:14558): (C-type lectin domain containing 7A) This gene encodes a member of the C-type lectin/C-type lectin-like domain (CTL/CTLD) superfamily. The encoded glycoprotein is a small type II membrane receptor with an extracellular C-type lectin-like domain fold and a cytoplasmic domain with an immunoreceptor tyrosine-based activation motif. It functions as a pattern-recognition receptor that recognizes a variety of beta-1,3-linked and beta-1,6-linked glucans from fungi and plants, and in this way plays a role in innate immune response. Alternate transcriptional splice variants, encoding different isoforms, have been characterized. This gene is closely linked to other CTL/CTLD superfamily members on chromosome 12p13 in the natural killer gene complex region. [provided by RefSeq, Jul 2008]

CLEC7A Gene-Disease associations (from GenCC):

• chronic mucocutaneous candidiasis

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000299754 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_197947.3. 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
	CLEC7A	NM_197947.3	MANE Select	c.714T>A	p.Tyr238*	stop_gained	Exon 6 of 6	NP_922938.1	Q9BXN2-1
	CLEC7A	NM_022570.5		c.576T>A	p.Tyr192*	stop_gained	Exon 5 of 5	NP_072092.2
	CLEC7A	NM_197950.3		c.477T>A	p.Tyr159*	stop_gained	Exon 4 of 4	NP_922941.1	Q9BXN2-5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLEC7A	ENST00000304084.13	TSL:1 MANE Select	c.714T>A	p.Tyr238*	stop_gained	Exon 6 of 6	ENSP00000302569.8	Q9BXN2-1
	CLEC7A	ENST00000353231.9	TSL:1	c.576T>A	p.Tyr192*	stop_gained	Exon 5 of 5	ENSP00000266456.6	Q9BXN2-2
	CLEC7A	ENST00000396484.6	TSL:1	c.477T>A	p.Tyr159*	stop_gained	Exon 4 of 4	ENSP00000379743.2	Q9BXN2-5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.36	D
BayesDel_noAF	Pathogenic	0.28
CADD	Pathogenic	36
DANN	Uncertain	0.98
Eigen	Benign	-0.082
Eigen_PC	Benign	-0.39
FATHMM_MKL	Benign	0.18	N
PhyloP100		-0.069
Vest4		0.34
GERP RS		-2.3
Mutation Taster		=181/19	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: rs16910526; hg19: chr12-10271087;