Variant 19-51643547-A-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.1138T>C(p.Tyr380His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000552 in 1,520,646 control chromosomes in the GnomAD database, including 130 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00028 ( 5 hom., cov: 23)

Exomes 𝑓: 0.00058 ( 125 hom. )

Consequence

SIGLEC14
NM_001098612.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.47

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=0.12582907).

BS2

High Homozygotes in GnomAd4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SIGLEC14	NM_001098612.3 linkuse as main transcript	c.1138T>C	p.Tyr380His	missense_variant	6/7	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.1138T>C	p.Tyr380His	missense_variant	6/7	1	NM_001098612.3	ENSP00000354090	P1
SIGLEC14	ENST00000533866.1 linkuse as main transcript	n.485T>C		non_coding_transcript_exon_variant	3/5	4

Frequencies

GnomAD3 genomes

AF:

0.000279

AC:

AN:

132644

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000173

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:

0.000493

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000215

AC:

AN:

228400

Hom.:

AF XY:

0.000249

AC XY:

AN XY:

124292

show subpopulations

Gnomad AFR exome

AF:

0.0000714

Gnomad AMR exome

AF:

0.0000299

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:

0.000430

Gnomad OTH exome

AF:

0.000176

GnomAD4 exome

AF:

0.000578

AC:

802

AN:

1387910

Hom.:

125

Cov.:

AF XY:

0.000565

AC XY:

390

AN XY:

689770

show subpopulations

Gnomad4 AFR exome

AF:

0.0000650

Gnomad4 AMR exome

AF:

0.0000693

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000405

Gnomad4 NFE exome

AF:

0.000688

Gnomad4 OTH exome

AF:

0.00101

GnomAD4 genome

AF:

0.000279

AC:

AN:

132736

Hom.:

Cov.:

AF XY:

0.000281

AC XY:

AN XY:

64092

show subpopulations

Gnomad4 AFR

AF:

0.000173

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:

0.000494

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000424

Hom.:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000378

AC:

ExAC

AF:

0.000310

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

Jul 14, 2021

The c.1138T>C (p.Y380H) alteration is located in exon 6 (coding exon 6) of the SIGLEC14 gene. This alteration results from a T to C substitution at nucleotide position 1138, causing the tyrosine (Y) at amino acid position 380 to be replaced by a histidine (H). 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

Uncertain

0.44

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.43

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.042

Eigen

Benign

-0.016

Eigen_PC

Benign

-0.022

FATHMM_MKL

Benign

0.61

LIST_S2

Benign

0.65

M_CAP

Benign

0.0097

MetaRNN

Benign

0.13

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.8

MutationTaster

Benign

1.0

N;D

PrimateAI

Uncertain

0.70

PROVEAN

Benign

-1.6

REVEL

Benign

0.14

Sift

Uncertain

0.010

Sift4G

Benign

0.11

Polyphen

0.90

Vest4

0.47

MVP

0.12

MPC

0.64

ClinPred

0.073

GERP RS

2.6

Varity_R

0.15

gMVP

0.34

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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