chr19-51644024-A-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -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. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L256V) has been classified 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

Publications

0 publications found

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:

SIGLEC5 (HGNC:10874): (sialic acid binding Ig like lectin 5) This gene encodes a member of the sialic acid-binding immunoglobulin-like lectin (Siglec) family. These cell surface lectins are characterized by structural motifs in the immunoglobulin (Ig)-like domains and sialic acid recognition sites in the first Ig V set domain. The encoded protein is a member of the CD33-related subset of Siglecs and inhibits the activation of several cell types including monocytes, macrophages and neutrophils. Binding of group B Streptococcus (GBS) to the encoded protein plays a role in GBS immune evasion. [provided by RefSeq, Feb 2012]

SIGLEC5 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

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

BS2

High Homozygotes in GnomAd4 at 10 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001098612.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SIGLEC14	NM_001098612.3	MANE Select	c.767T>C	p.Leu256Pro	missense	Exon 5 of 7	NP_001092082.1	Q08ET2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SIGLEC14	ENST00000360844.7	TSL:1 MANE Select	c.767T>C	p.Leu256Pro	missense	Exon 5 of 7	ENSP00000354090.5	Q08ET2
SIGLEC14	ENST00000533866.1	TSL:4	n.114T>C		non_coding_transcript_exon	Exon 2 of 5
SIGLEC5	ENST00000534261.4	TSL:5	n.69+1453T>C		intron	N/A

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

GnomAD2 exomes

AF:

0.000327

AC:

AN:

211008

AF XY:

0.000281

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 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

African (AFR)

AF:

0.0000328

AC:

AN:

30462

American (AMR)

AF:

0.0000965

AC:

AN:

41470

Ashkenazi Jewish (ASJ)

AF:

0.0000417

AC:

AN:

23968

East Asian (EAS)

AF:

0.00

AC:

AN:

25554

South Asian (SAS)

AF:

0.00

AC:

AN:

75868

European-Finnish (FIN)

AF:

0.000244

AC:

AN:

49116

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5460

European-Non Finnish (NFE)

AF:

0.000723

AC:

770

AN:

1064518

Other (OTH)

AF:

0.000445

AC:

AN:

56136

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

115

154

192

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

104

130

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000445

AC:

AN:

139182

Hom.:

Cov.:

AF XY:

0.000460

AC XY:

AN XY:

67356

show subpopulations

African (AFR)

AF:

0.0000544

AC:

AN:

36740

American (AMR)

AF:

0.000207

AC:

AN:

14458

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3326

East Asian (EAS)

AF:

0.00

AC:

AN:

2978

South Asian (SAS)

AF:

0.00

AC:

AN:

4082

European-Finnish (FIN)

AF:

0.000312

AC:

AN:

9628

Middle Eastern (MID)

AF:

0.00

AC:

AN:

306

European-Non Finnish (NFE)

AF:

0.000832

AC:

AN:

64866

Other (OTH)

AF:

0.00

AC:

AN:

1952

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.510

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.41

CADD

Benign

(source)

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

PhyloP100

0.24

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

Mutation Taster

=100/0

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over