19-7729422-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_198492.4(CLEC4G):​c.826G>A​(p.Ala276Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000689 in 1,450,598 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)
Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

CLEC4G
NM_198492.4 missense

Scores

4
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.585
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.3654549).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
CLEC4GNM_198492.4 linkuse as main transcriptc.826G>A p.Ala276Thr missense_variant 9/9 ENST00000328853.11 NP_940894.1 Q6UXB4Q08G24Q6XYD1
CLEC4GNM_001244856.2 linkuse as main transcriptc.790G>A p.Ala264Thr missense_variant 9/9 NP_001231785.1 B7ZKQ2Q08G24Q6XYD1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
CLEC4GENST00000328853.11 linkuse as main transcriptc.826G>A p.Ala276Thr missense_variant 9/91 NM_198492.4 ENSP00000327599.4 Q6UXB4
ENSG00000288669ENST00000678003.1 linkuse as main transcriptn.*1371G>A non_coding_transcript_exon_variant 13/13 ENSP00000504497.1 A0A7I2YQT4
ENSG00000288669ENST00000678003.1 linkuse as main transcriptn.*1371G>A 3_prime_UTR_variant 13/13 ENSP00000504497.1 A0A7I2YQT4

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD4 exome
AF:
6.89e-7
AC:
1
AN:
1450598
Hom.:
0
Cov.:
27
AF XY:
0.00000138
AC XY:
1
AN XY:
722368
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
9.08e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
31

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsFeb 27, 2024The c.826G>A (p.A276T) alteration is located in exon 9 (coding exon 9) of the CLEC4G gene. This alteration results from a G to A substitution at nucleotide position 826, causing the alanine (A) at amino acid position 276 to be replaced by a threonine (T). 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
0.32
BayesDel_addAF
Benign
-0.28
T
BayesDel_noAF
Benign
-0.64
CADD
Uncertain
23
DANN
Uncertain
1.0
DEOGEN2
Benign
0.048
T
Eigen
Benign
-0.24
Eigen_PC
Benign
-0.33
FATHMM_MKL
Benign
0.26
N
LIST_S2
Benign
0.61
T
M_CAP
Benign
0.0044
T
MetaRNN
Benign
0.37
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.6
L
MutationTaster
Benign
1.0
N
PrimateAI
Uncertain
0.61
T
PROVEAN
Uncertain
-3.0
D
REVEL
Benign
0.075
Sift
Benign
1.0
T
Sift4G
Uncertain
0.051
T
Polyphen
1.0
D
Vest4
0.44
MutPred
0.36
Loss of catalytic residue at A276 (P = 0.0455);
MVP
0.41
MPC
1.4
ClinPred
0.94
D
GERP RS
2.0
Varity_R
0.12
gMVP
0.75

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1014021042; hg19: chr19-7794308; API