Variant 19-51646612-C-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001098612.3(SIGLEC14):c.66G>T(p.Glu22Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000023 ( 0 hom., cov: 6)

Exomes 𝑓: 0.00025 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

SIGLEC14
NM_001098612.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0150

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 -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.100628585).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SIGLEC14	NM_001098612.3 linkuse as main transcript	c.66G>T	p.Glu22Asp	missense_variant	2/7	ENST00000360844.7	NP_001092082.1
SIGLEC14	XM_047437991.1 linkuse as main transcript	c.66G>T	p.Glu22Asp	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.66G>T	p.Glu22Asp	missense_variant	2/7	1	NM_001098612.3	ENSP00000354090	P1

Frequencies

GnomAD3 genomes

AF:

0.0000235

AC:

AN:

42630

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.0000460

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000179

AC:

AN:

55950

Hom.:

AF XY:

0.000286

AC XY:

AN XY:

27968

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000931

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000128

Gnomad SAS exome

AF:

0.00130

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000249

AC:

121

AN:

486304

Hom.:

Cov.:

AF XY:

0.000377

AC XY:

AN XY:

254572

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000524

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000329

Gnomad4 SAS exome

AF:

0.00181

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000115

Gnomad4 OTH exome

AF:

0.0000369

GnomAD4 genome

AF:

0.0000235

AC:

AN:

42630

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

17810

show subpopulations

Gnomad4 AFR

AF:

0.00

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:

0.0000460

Gnomad4 OTH

AF:

0.00

ExAC

AF:

0.0000795

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

Aug 30, 2021

The c.66G>T (p.E22D) alteration is located in exon 2 (coding exon 2) of the SIGLEC14 gene. This alteration results from a G to T substitution at nucleotide position 66, causing the glutamic acid (E) at amino acid position 22 to be replaced by an aspartic acid (D). 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

0.20

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.63

CADD

Benign

DANN

Benign

0.95

DEOGEN2

Benign

0.033

.;T

Eigen

Benign

-0.86

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.039

LIST_S2

Benign

0.28

.;T

M_CAP

Benign

0.012

MetaRNN

Benign

0.10

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.8

.;M

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.48

PROVEAN

Benign

-1.7

.;N

REVEL

Benign

0.024

Sift

Benign

0.22

.;T

Sift4G

Benign

0.42

T;T

Polyphen

0.44

.;B

Vest4

0.081

MutPred

0.24

Loss of ubiquitination at K27 (P = 0.1139);Loss of ubiquitination at K27 (P = 0.1139);

MVP

0.33

MPC

1.7

ClinPred

0.045

GERP RS

-1.7

Varity_R

0.12

gMVP

0.12

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