NM_197947.3:c.397C>T

Variant names:

• chr12-10125392-G-A
• rs144190589
• NM_197947.3:c.397C>T

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_197947.3(CLEC7A):​c.397C>T​(p.Leu133Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00867 in 1,613,232 control chromosomes in the GnomAD database, including 89 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0063 (4 hom., cov: 32)
  • Exomes 𝑓: 0.0089 (85 hom.)
• Consequence: CLEC7A NM_197947.3 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.684
• Publications: 6 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: Benign. The variant received -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BP6: Variant 12-10125392-G-A is Benign according to our data. Variant chr12-10125392-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 789214.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.684 with no splicing effect.
• BS2: High AC in GnomAd4 at 955 AD gene.

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.397C>T	p.Leu133Leu	synonymous	Exon 4 of 6	NP_922938.1	Q9BXN2-1
	CLEC7A	NM_022570.5		c.259C>T	p.Leu87Leu	synonymous	Exon 3 of 5	NP_072092.2
	CLEC7A	NM_197948.3		c.397C>T	p.Leu133Leu	synonymous	Exon 4 of 5	NP_922939.1	Q9BXN2-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLEC7A	ENST00000304084.13	TSL:1 MANE Select	c.397C>T	p.Leu133Leu	synonymous	Exon 4 of 6	ENSP00000302569.8	Q9BXN2-1
	CLEC7A	ENST00000353231.9	TSL:1	c.259C>T	p.Leu87Leu	synonymous	Exon 3 of 5	ENSP00000266456.6	Q9BXN2-2
	CLEC7A	ENST00000533022.5	TSL:1	c.397C>T	p.Leu133Leu	synonymous	Exon 4 of 5	ENSP00000431461.1	Q9BXN2-3

Frequencies

GnomAD3 genomes AF: 0.00629 AC: 956 AN: 152068 Hom.: 4 Cov.: 32

Gnomad AFR AF: 0.00164

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.00249

Gnomad ASJ AF: 0.000865

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0131

Gnomad FIN AF: 0.0114

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00959

Gnomad OTH AF: 0.00431

GnomAD2 exomes AF: 0.00724 AC: 1818 AN: 251038 AF XY: 0.00761

Gnomad AFR exome AF: 0.00178

Gnomad AMR exome AF: 0.00203

Gnomad ASJ exome AF: 0.000794

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0109

Gnomad NFE exome AF: 0.00936

Gnomad OTH exome AF: 0.00718

GnomAD4 exome AF: 0.00892 AC: 13030 AN: 1461046 Hom.: 85 Cov.: 31 AF XY: 0.00900 AC XY: 6543 AN XY: 726860

African (AFR) AF: 0.00120 AC: 40 AN: 33470

American (AMR) AF: 0.00217 AC: 97 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.000842 AC: 22 AN: 26126

East Asian (EAS) AF: 0.00 AC: 0 AN: 39676

South Asian (SAS) AF: 0.0120 AC: 1031 AN: 86250

European-Finnish (FIN) AF: 0.0105 AC: 555 AN: 53018

Middle Eastern (MID) AF: 0.00745 AC: 43 AN: 5768

European-Non Finnish (NFE) AF: 0.00969 AC: 10776 AN: 1111650

Other (OTH) AF: 0.00772 AC: 466 AN: 60370

GnomAD4 genome AF: 0.00628 AC: 955 AN: 152186 Hom.: 4 Cov.: 32 AF XY: 0.00625 AC XY: 465 AN XY: 74414

African (AFR) AF: 0.00164 AC: 68 AN: 41530

American (AMR) AF: 0.00249 AC: 38 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.000865 AC: 3 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5170

South Asian (SAS) AF: 0.0129 AC: 62 AN: 4816

European-Finnish (FIN) AF: 0.0114 AC: 121 AN: 10596

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00959 AC: 652 AN: 68002

Other (OTH) AF: 0.00426 AC: 9 AN: 2112

Alfa AF: 0.00614 Hom.: 4

Bravo AF: 0.00508

Asia WGS AF: 0.00375 AC: 13 AN: 3478

EpiCase AF: 0.00812

EpiControl AF: 0.00747

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	1	Familial chronic mucocutaneous candidiasis;C3279774:Aspergillosis, susceptibility to (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	3.9
DANN	Benign	0.67
PhyloP100		0.68
Mutation Taster		=100/0	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: rs144190589; hg19: chr12-10277991; COSMIC: COSV105880501; COSMIC: COSV105880501;