Variant 19-51643372-C-T 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.1174G>A(p.Ala392Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00014 in 1,523,314 control chromosomes in the GnomAD database, including 22 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/23 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00019 ( 2 hom., cov: 22)

Exomes 𝑓: 0.00014 ( 20 hom. )

Consequence

SIGLEC14
NM_001098612.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -2.20

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SIGLEC14	NM_001098612.3 linkuse as main transcript	c.1174G>A	p.Ala392Thr	missense_variant	7/7	ENST00000360844.7	NP_001092082.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SIGLEC14	ENST00000360844.7 linkuse as main transcript	c.1174G>A	p.Ala392Thr	missense_variant	7/7	1	NM_001098612.3	ENSP00000354090	P1
SIGLEC14	ENST00000533866.1 linkuse as main transcript	n.521G>A		non_coding_transcript_exon_variant	4/5	4

Frequencies

GnomAD3 genomes

AF:

0.000187

AC:

AN:

133898

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000287

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000285

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000258

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00974

Gnomad NFE

AF:

0.000252

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000137

AC:

AN:

226162

Hom.:

AF XY:

0.000114

AC XY:

AN XY:

123072

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000600

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000252

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000160

Gnomad OTH exome

AF:

0.000888

GnomAD4 exome

AF:

0.000135

AC:

188

AN:

1389318

Hom.:

Cov.:

AF XY:

0.000136

AC XY:

AN XY:

690442

show subpopulations

Gnomad4 AFR exome

AF:

0.000296

Gnomad4 AMR exome

AF:

0.000139

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000152

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000977

Gnomad4 OTH exome

AF:

0.000422

GnomAD4 genome

AF:

0.000187

AC:

AN:

133996

Hom.:

Cov.:

AF XY:

0.000170

AC XY:

AN XY:

64588

show subpopulations

Gnomad4 AFR

AF:

0.0000286

Gnomad4 AMR

AF:

0.000285

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000258

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000252

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000161

Hom.:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000125

AC:

ExAC

AF:

0.000114

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

Nov 10, 2022

The c.1174G>A (p.A392T) alteration is located in exon 7 (coding exon 7) of the SIGLEC14 gene. This alteration results from a G to A substitution at nucleotide position 1174, causing the alanine (A) at amino acid position 392 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

0.090

BayesDel_addAF

Benign

-0.60

BayesDel_noAF

Benign

-0.80

CADD

Benign

0.58

DANN

Benign

0.73

DEOGEN2

Benign

0.0034

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.0050

LIST_S2

Benign

0.37

M_CAP

Benign

0.0016

MetaRNN

Benign

0.034

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.41

PROVEAN

Benign

-0.13

REVEL

Benign

0.028

Sift

Uncertain

0.029

Sift4G

Uncertain

0.043

Polyphen

0.0

Vest4

0.0090

MVP

0.014

MPC

0.12

ClinPred

0.035

GERP RS

-2.7

Varity_R

0.043

gMVP

0.074

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.24

Details are displayed if max score is > 0.2

DS_DG_spliceai

0.24

Position offset: -44

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