Variant 19-51646347-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_001098612.3(SIGLEC14):c.331G>C(p.Glu111Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000374 in 1,240,826 control chromosomes in the GnomAD database, including 67 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00020 ( 0 hom., cov: 9)

Exomes 𝑓: 0.00038 ( 67 hom. )

Consequence

SIGLEC14
NM_001098612.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.618

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 -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.12751442).

BS2

High Homozygotes in GnomAdExome4 at 67 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SIGLEC14	NM_001098612.3 linkuse as main transcript	c.331G>C	p.Glu111Gln	missense_variant	2/7	ENST00000360844.7	NP_001092082.1	Q08ET2
SIGLEC14	XM_047437991.1 linkuse as main transcript	c.331G>C	p.Glu111Gln	missense_variant	2/5		XP_047293947.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SIGLEC14	ENST00000360844.7 linkuse as main transcript	c.331G>C	p.Glu111Gln	missense_variant	2/7	1	NM_001098612.3	ENSP00000354090.5		Q08ET2

Frequencies

GnomAD3 genomes

AF:

0.000205

AC:

AN:

73252

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000198

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000302

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000192

AC:

AN:

208780

Hom.:

AF XY:

0.000230

AC XY:

AN XY:

112946

show subpopulations

Gnomad AFR exome

AF:

0.000236

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:

0.000376

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000385

AC:

449

AN:

1167574

Hom.:

Cov.:

AF XY:

0.000384

AC XY:

225

AN XY:

585738

show subpopulations

Gnomad4 AFR exome

AF:

0.000248

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:

0.000466

Gnomad4 OTH exome

AF:

0.000598

GnomAD4 genome

AF:

0.000205

AC:

AN:

73252

Hom.:

Cov.:

AF XY:

0.000175

AC XY:

AN XY:

34298

show subpopulations

Gnomad4 AFR

AF:

0.000198

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000302

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000223

Hom.:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000387

AC:

ExAC

AF:

0.000183

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

Dec 13, 2021

The c.331G>C (p.E111Q) 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 331, causing the glutamic acid (E) at amino acid position 111 to be replaced by a glutamine (Q). 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

0.11

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.65

CADD

Benign

2.3

DANN

Benign

0.48

DEOGEN2

Benign

0.0086

.;T

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.013

LIST_S2

Benign

0.057

.;T

M_CAP

Benign

0.012

MetaRNN

Benign

0.13

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.7

.;L

PrimateAI

Benign

0.21

PROVEAN

Benign

-0.040

.;N

REVEL

Benign

0.035

Sift

Benign

0.55

.;T

Sift4G

Benign

0.56

T;T

Polyphen

0.34

.;B

Vest4

0.087

MVP

0.23

MPC

2.0

ClinPred

0.017

GERP RS

-4.4

Varity_R

0.053

gMVP

0.17

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