19-51646488-C-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001098612.3(SIGLEC14):ā€‹c.190G>Cā€‹(p.Gly64Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. 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 (ā˜…).

Frequency

Genomes: not found (cov: 5)
Exomes š‘“: 0.0 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

SIGLEC14
NM_001098612.3 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.26
Variant links:
Genes affected
SIGLEC14 (HGNC:32926): (sialic acid binding Ig like lectin 14) Predicted to enable sialic acid binding activity. Predicted to be involved in cell adhesion. Predicted to be located in ficolin-1-rich granule membrane and tertiary granule membrane. Predicted to be active in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.16117486).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
SIGLEC14NM_001098612.3 linkuse as main transcriptc.190G>C p.Gly64Arg missense_variant 2/7 ENST00000360844.7 NP_001092082.1 Q08ET2
SIGLEC14XM_047437991.1 linkuse as main transcriptc.190G>C p.Gly64Arg missense_variant 2/5 XP_047293947.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
SIGLEC14ENST00000360844.7 linkuse as main transcriptc.190G>C p.Gly64Arg missense_variant 2/71 NM_001098612.3 ENSP00000354090.5 Q08ET2

Frequencies

GnomAD3 genomes
Cov.:
5
GnomAD4 exome
Data not reliable, filtered out with message: AC0;AS_VQSR
AF:
0.00
AC:
0
AN:
587726
Hom.:
0
Cov.:
7
AF XY:
0.00
AC XY:
0
AN XY:
305562
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:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
5

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 GeneticsDec 09, 2023The c.190G>C (p.G64R) alteration is located in exon 2 (coding exon 2) of the SIGLEC14 gene. This alteration results from a G to C substitution at nucleotide position 190, causing the glycine (G) at amino acid position 64 to be replaced by an arginine (R). 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
0.12
BayesDel_addAF
Benign
-0.23
T
BayesDel_noAF
Benign
-0.56
CADD
Benign
0.37
DANN
Benign
0.67
DEOGEN2
Benign
0.11
.;T
Eigen
Benign
-0.93
Eigen_PC
Benign
-1.1
FATHMM_MKL
Benign
0.015
N
LIST_S2
Benign
0.51
.;T
M_CAP
Benign
0.0078
T
MetaRNN
Benign
0.16
T;T
MetaSVM
Benign
-0.94
T
MutationAssessor
Benign
0.98
.;L
PrimateAI
Benign
0.27
T
PROVEAN
Pathogenic
-5.7
.;D
REVEL
Benign
0.077
Sift
Benign
0.15
.;T
Sift4G
Benign
0.36
T;T
Polyphen
0.22
.;B
Vest4
0.10
MutPred
0.56
Loss of catalytic residue at I66 (P = 0.2285);Loss of catalytic residue at I66 (P = 0.2285);
MVP
0.35
MPC
2.2
ClinPred
0.38
T
GERP RS
-0.39
Varity_R
0.19
gMVP
0.29

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: chr19-52149741; API