chr12-7741427-T-A

Variant names:

• chr12-7741427-T-A
• rs150641216
• NM_001371390.1:c.229A>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001371390.1(CLEC4C):​c.229A>T​(p.Ile77Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000703 in 1,423,250 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I77V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: CLEC4C NM_001371390.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.246
• Publications: 0 publications found

Genes affected

CLEC4C (HGNC:13258): (C-type lectin domain family 4 member C) 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 play a role in dendritic cell function. Two transcript variants encoding distinct isoforms have been identified for this gene. [provided by RefSeq, Jul 2008]

CLEC4C Gene-Disease associations (from GenCC):

• amyotrophic lateral sclerosis

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.21627298).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001371390.1. 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
	CLEC4C	NM_001371390.1	MANE Select	c.229A>T	p.Ile77Leu	missense	Exon 3 of 6	NP_001358319.1	Q8WTT0-1
	CLEC4C	NM_130441.3		c.229A>T	p.Ile77Leu	missense	Exon 4 of 7	NP_569708.1	Q8WTT0-1
	CLEC4C	NM_203503.2		c.136A>T	p.Ile46Leu	missense	Exon 3 of 6	NP_987099.1	Q8WTT0-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLEC4C	ENST00000360345.8	TSL:1 MANE Select	c.229A>T	p.Ile77Leu	missense	Exon 3 of 6	ENSP00000353500.3	Q8WTT0-1
	CLEC4C	ENST00000542353.5	TSL:1	c.229A>T	p.Ile77Leu	missense	Exon 4 of 7	ENSP00000440428.1	Q8WTT0-1
	CLEC4C	ENST00000540085.5	TSL:1	c.136A>T	p.Ile46Leu	missense	Exon 2 of 5	ENSP00000445338.1	Q8WTT0-2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.03e-7 AC: 1 AN: 1423250 Hom.: 0 Cov.: 25 AF XY: 0.00 AC XY: 0 AN XY: 710574

African (AFR) AF: 0.00 AC: 0 AN: 32908

American (AMR) AF: 0.00 AC: 0 AN: 44658

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25842

East Asian (EAS) AF: 0.00 AC: 0 AN: 39542

South Asian (SAS) AF: 0.00 AC: 0 AN: 85602

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53406

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5692

European-Non Finnish (NFE) AF: 9.29e-7 AC: 1 AN: 1076460

Other (OTH) AF: 0.00 AC: 0 AN: 59140

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.070
BayesDel_addAF	Benign	-0.43	T
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.47
DANN	Benign	0.73
DEOGEN2	Benign	0.0024	T
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.0028	N
LIST_S2	Benign	0.16	T
M_CAP	Benign	0.00092	T
MetaRNN	Benign	0.22	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	-1.6	N
PhyloP100		-0.25
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-0.10	N
REVEL	Benign	0.077
Sift	Benign	0.33	T
Sift4G	Benign	0.64	T
Polyphen		0.0	B
Vest4		0.15
MutPred		0.75		Gain of relative solvent accessibility (P = 0.0479)
MVP		0.099
MPC		0.35
ClinPred		0.069	T
GERP RS		-3.6
Varity_R		0.21
gMVP		0.13
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs150641216; hg19: chr12-7894023;