Variant chr19-51644024-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001098612.3(SIGLEC14):c.767T>C(p.Leu256Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000579 in 1,511,734 control chromosomes in the GnomAD database, including 123 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00045 ( 10 hom., cov: 25)

Exomes 𝑓: 0.00059 ( 113 hom. )

Consequence

SIGLEC14
NM_001098612.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.244

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:

SIGLEC14 (HGNC:):

SIGLEC14 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.04541129).

BS2

High Homozygotes in GnomAd4 at 10 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SIGLEC14	NM_001098612.3 linkuse as main transcript	c.767T>C	p.Leu256Pro	missense_variant	5/7	ENST00000360844.7	NP_001092082.1	Q08ET2
SIGLEC14	XM_047437991.1 linkuse as main transcript	c.730T>C	p.Ter244Argext*?	stop_lost	5/5		XP_047293947.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
SIGLEC14	ENST00000360844.7 linkuse as main transcript	c.767T>C	p.Leu256Pro	missense_variant	5/7	1	NM_001098612.3	ENSP00000354090.5	Q08ET2
SIGLEC14	ENST00000533866.1 linkuse as main transcript	n.114T>C		non_coding_transcript_exon_variant	2/5	4
SIGLEC5	ENST00000534261.4 linkuse as main transcript	n.69+1453T>C		intron_variant		5

Frequencies

GnomAD3 genomes

AF:

0.000445

AC:

AN:

139182

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000544

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000207

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000312

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000832

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000327

AC:

AN:

211008

Hom.:

AF XY:

0.000281

AC XY:

AN XY:

113970

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000636

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000538

Gnomad NFE exome

AF:

0.000652

Gnomad OTH exome

AF:

0.000191

GnomAD4 exome

AF:

0.000592

AC:

813

AN:

1372552

Hom.:

113

Cov.:

AF XY:

0.000531

AC XY:

361

AN XY:

679344

show subpopulations

Gnomad4 AFR exome

AF:

0.0000328

Gnomad4 AMR exome

AF:

0.0000965

Gnomad4 ASJ exome

AF:

0.0000417

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000244

Gnomad4 NFE exome

AF:

0.000723

Gnomad4 OTH exome

AF:

0.000445

GnomAD4 genome

AF:

0.000445

AC:

AN:

139182

Hom.:

Cov.:

AF XY:

0.000460

AC XY:

AN XY:

67356

show subpopulations

Gnomad4 AFR

AF:

0.0000544

Gnomad4 AMR

AF:

0.000207

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000312

Gnomad4 NFE

AF:

0.000832

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000476

Hom.:

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000245

AC:

ExAC

AF:

0.000373

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

Mar 04, 2024

The c.767T>C (p.L256P) alteration is located in exon 5 (coding exon 5) of the SIGLEC14 gene. This alteration results from a T to C substitution at nucleotide position 767, causing the leucine (L) at amino acid position 256 to be replaced by a proline (P). 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

-0.41

BayesDel_noAF

Benign

-0.41

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.11

Eigen

Benign

-0.64

Eigen_PC

Benign

-0.74

FATHMM_MKL

Benign

0.051

LIST_S2

Benign

0.33

M_CAP

Benign

0.0035

MetaRNN

Benign

0.045

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.6

PrimateAI

Benign

0.29

PROVEAN

Pathogenic

-4.4

REVEL

Benign

0.10

Sift

Benign

0.073

Sift4G

Benign

0.14

Polyphen

0.29

Vest4

0.25

MVP

0.16

MPC

0.24

ClinPred

0.079

GERP RS

2.9

Varity_R

0.43

gMVP

0.66

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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