Variant 19-51643627-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_001098612.3(SIGLEC14):c.1058C>T(p.Ser353Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000717 in 1,394,754 control chromosomes in the GnomAD database, including 2 homozygotes. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 24)

Exomes 𝑓: 0.0000072 ( 2 hom. )

Consequence

SIGLEC14
NM_001098612.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.38

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]

SIGLEC14 links:

SIGLEC5 (HGNC:10874): (sialic acid binding Ig like lectin 5) This gene encodes a member of the sialic acid-binding immunoglobulin-like lectin (Siglec) family. These cell surface lectins are characterized by structural motifs in the immunoglobulin (Ig)-like domains and sialic acid recognition sites in the first Ig V set domain. The encoded protein is a member of the CD33-related subset of Siglecs and inhibits the activation of several cell types including monocytes, macrophages and neutrophils. Binding of group B Streptococcus (GBS) to the encoded protein plays a role in GBS immune evasion. [provided by RefSeq, Feb 2012]

SIGLEC5 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SIGLEC14	NM_001098612.3 link	c.1058C>T	p.Ser353Phe	missense_variant	6/7	ENST00000360844.7	NP_001092082.1	Q08ET2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
SIGLEC14	ENST00000360844.7 link	c.1058C>T	p.Ser353Phe	missense_variant	6/7	1	NM_001098612.3	ENSP00000354090.5	Q08ET2
SIGLEC14	ENST00000533866.1 link	n.405C>T		non_coding_transcript_exon_variant	3/5	4
SIGLEC5	ENST00000534261.4 link	n.69+1850C>T		intron_variant		5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000433

AC:

AN:

231102

Hom.:

AF XY:

0.00

AC XY:

AN XY:

125422

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000921

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000717

AC:

AN:

1394754

Hom.:

Cov.:

AF XY:

0.00000721

AC XY:

AN XY:

693122

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:

0.00000929

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000879

AC:

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 submitter

clinical testing

Ambry Genetics

Oct 04, 2024

The c.1058C>T (p.S353F) alteration is located in exon 6 (coding exon 6) of the SIGLEC14 gene. This alteration results from a C to T substitution at nucleotide position 1058, causing the serine (S) at amino acid position 353 to be replaced by a phenylalanine (F). 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

0.19

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Benign

-0.41

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.029

Eigen

Benign

0.14

Eigen_PC

Benign

0.061

FATHMM_MKL

Benign

0.55

LIST_S2

Benign

0.65

M_CAP

Benign

0.0053

MetaRNN

Uncertain

0.53

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.8

PrimateAI

Benign

0.38

PROVEAN

Benign

-2.2

REVEL

Benign

0.12

Sift

Uncertain

0.0060

Sift4G

Uncertain

0.044

Polyphen

0.99

Vest4

0.52

MutPred

0.41

Loss of ubiquitination at K349 (P = 0.0665);

MVP

0.42

MPC

0.27

ClinPred

0.47

GERP RS

2.3

Varity_R

0.094

gMVP

0.27

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over