19-7730060-C-A

Position:

• chr19-7730060-C-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_198492.4(CLEC4G):​c.586G>T​(p.Ala196Ser) 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 Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CLEC4G NM_198492.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -2.49

Genes affected

CLEC4G (HGNC:24591): (C-type lectin domain family 4 member G) This gene encodes a glycan-binding receptor and member of the C-type lectin family which plays a role in the immune response. C-type lectin receptors are pattern recognition receptors located on immune cells that play a role in the recognition and uptake of both self and non-self glycoproteins as well as mediating cell adhesion, glycoprotein clearance, and cell signaling functions. This gene's protein binds complex-type N-glycans of the viral envelope proteins of Ebola virus, West Nile filovirus, and SARS coronavirus, but not HIV or hepatitis C virus. In mouse, this protein has been shown to recognize activated T-cells and to negatively regulate T-cell receptor-mediated signalling. It also acts as a novel, liver-specific regulator of NK cell-mediated immunity in mouse. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Apr 2020]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.05402094).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CLEC4G	NM_198492.4	c.586G>T	p.Ala196Ser	missense_variant	7/9	ENST00000328853.11	NP_940894.1
CLEC4G	NM_001244856.2	c.550G>T	p.Ala184Ser	missense_variant	7/9		NP_001231785.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CLEC4G	ENST00000328853.11	c.586G>T	p.Ala196Ser	missense_variant	7/9	1	NM_198492.4	ENSP00000327599	P1
CLEC4G	ENST00000676742.1	c.523G>T	p.Ala175Ser	missense_variant	6/8			ENSP00000504187
CLEC4G	ENST00000678118.1	c.586G>T	p.Ala196Ser	missense_variant	7/8			ENSP00000503869

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 38

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 05, 2023

The c.586G>T (p.A196S) alteration is located in exon 7 (coding exon 7) of the CLEC4G gene. This alteration results from a G to T substitution at nucleotide position 586, causing the alanine (A) at amino acid position 196 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.090
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.79
CADD	Benign	0.10
DANN	Benign	0.61
DEOGEN2	Benign	0.030	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.034	N
LIST_S2	Benign	0.52	T
M_CAP	Benign	0.0044	T
MetaRNN	Benign	0.054	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.86	L
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-0.71	N
REVEL	Benign	0.082
Sift	Benign	0.70	T
Sift4G	Benign	0.72	T
Polyphen		0.023	B
Vest4		0.12
MutPred		0.51		Loss of sheet (P = 0.007);
MVP		0.35
MPC		0.47
ClinPred		0.065	T
GERP RS		-11
Varity_R		0.056
gMVP		0.40

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: chr19-7794946;