chr12-8138264-G-A

Position:

• chr12-8138264-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 4P and 4B. PM1 PM2 BP4_Moderate BP6_Moderate

The NM_016184.4(CLEC4A):​c.691G>A​(p.Glu231Lys) 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. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: CLEC4A NM_016184.4 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.194

Genes affected

CLEC4A (HGNC:13257): (C-type lectin domain family 4 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 signalling, glycoprotein turnover, and roles in inflammation and immune response. The encoded type 2 transmembrane protein may play a role in inflammatory and immune response. Multiple transcript variants encoding distinct isoforms have been identified for this gene. 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]

ENSG00000284393 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM1: In a binding_site (size 0) in uniprot entity CLC4A_HUMAN
• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.12841079).
• BP6: Variant 12-8138264-G-A is Benign according to our data. Variant chr12-8138264-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3267691.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CLEC4A	NM_016184.4	c.691G>A	p.Glu231Lys	missense_variant	6/6	ENST00000229332.12	NP_057268.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CLEC4A	ENST00000229332.12	c.691G>A	p.Glu231Lys	missense_variant	6/6	1	NM_016184.4	ENSP00000229332.5
ENSG00000284393	ENST00000402465.8	n.113+11G>A		intron_variant		2		ENSP00000384896.4

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 31

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 28, 2024

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	9.4
DANN	Benign	0.94
DEOGEN2	Benign	0.0053	T;.;.;.
Eigen	Benign	-0.84
Eigen_PC	Benign	-0.73
FATHMM_MKL	Benign	0.083	N
LIST_S2	Benign	0.80	T;T;T;T
M_CAP	Benign	0.0037	T
MetaRNN	Benign	0.13	T;T;T;T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	0.57	N;.;.;.
MutationTaster	Benign	0.97	N;N;N;N
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-0.88	N;N;N;N
REVEL	Benign	0.088
Sift	Benign	0.70	T;T;T;T
Sift4G	Benign	0.62	T;T;T;T
Polyphen		0.18	B;B;B;B
Vest4		0.14
MutPred		0.70		Gain of MoRF binding (P = 1e-04);.;.;.;
MVP		0.28
MPC		0.29
ClinPred		0.13	T
GERP RS		-1.6
Varity_R		0.36
gMVP		0.76

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: chr12-8290860;