NM_197947.3:c.296C>T

Variant names:

• chr12-10126615-G-A
• rs368420045
• NM_197947.3:c.296C>T

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_197947.3(CLEC7A):​c.296C>T​(p.Ser99Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000167 in 1,612,784 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 𝑓 0.000013 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000017 (0 hom.)
• Consequence: CLEC7A NM_197947.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.25
• Publications: 0 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: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.18939984).
• BS2: High AC in GnomAdExome4 at 25 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.296C>T	p.Ser99Phe	missense	Exon 3 of 6	NP_922938.1	Q9BXN2-1
	CLEC7A	NM_197948.3		c.296C>T	p.Ser99Phe	missense	Exon 3 of 5	NP_922939.1	Q9BXN2-3
	CLEC7A	NM_022570.5		c.202+1132C>T		intron	N/A	NP_072092.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLEC7A	ENST00000304084.13	TSL:1 MANE Select	c.296C>T	p.Ser99Phe	missense	Exon 3 of 6	ENSP00000302569.8	Q9BXN2-1
	CLEC7A	ENST00000533022.5	TSL:1	c.296C>T	p.Ser99Phe	missense	Exon 3 of 5	ENSP00000431461.1	Q9BXN2-3
	CLEC7A	ENST00000353231.9	TSL:1	c.202+1132C>T		intron	N/A	ENSP00000266456.6	Q9BXN2-2

Frequencies

GnomAD3 genomes AF: 0.0000131 AC: 2 AN: 152162 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

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: 0.0000294

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000402 AC: 1 AN: 248480 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000886

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000171 AC: 25 AN: 1460622 Hom.: 0 Cov.: 31 AF XY: 0.0000151 AC XY: 11 AN XY: 726628

African (AFR) AF: 0.00 AC: 0 AN: 33382

American (AMR) AF: 0.00 AC: 0 AN: 44474

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26084

East Asian (EAS) AF: 0.00 AC: 0 AN: 39580

South Asian (SAS) AF: 0.00 AC: 0 AN: 86142

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53402

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5756

European-Non Finnish (NFE) AF: 0.0000225 AC: 25 AN: 1111476

Other (OTH) AF: 0.00 AC: 0 AN: 60326

GnomAD4 genome AF: 0.0000131 AC: 2 AN: 152162 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74328

African (AFR) AF: 0.00 AC: 0 AN: 41440

American (AMR) AF: 0.00 AC: 0 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10608

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

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68040

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000189

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000243 AC: 2

ExAC AF: 0.00000828 AC: 1

EpiCase AF: 0.0000547

EpiControl AF: 0.00

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	0.10
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.49
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.095	T
Eigen	Benign	0.052
Eigen_PC	Benign	0.065
FATHMM_MKL	Benign	0.71	D
LIST_S2	Benign	0.79	T
M_CAP	Benign	0.0052	T
MetaRNN	Benign	0.19	T
MetaSVM	Benign	-1.0	T
PhyloP100		2.3
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.078
Sift	Benign	0.039	D
Sift4G	Benign	0.28	T
Polyphen		0.83	P
Vest4		0.26
MVP		0.32
MPC		0.031
ClinPred		0.97	D
GERP RS		3.4
Varity_R		0.10
gMVP		0.51
Mutation Taster		=75/25	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: rs368420045; hg19: chr12-10279214;