dbSNP rs747638044: SIGLEC10:p.Asp133Tyr (chr19-51417106-C-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_033130.5(SIGLEC10):c.397G>T(p.Asp133Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,856 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

SIGLEC10
NM_033130.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.68

Variant links:

Genes affected

SIGLEC10 (HGNC:15620): (sialic acid binding Ig like lectin 10) SIGLECs are members of the immunoglobulin superfamily that are expressed on the cell surface. Most SIGLECs have 1 or more cytoplasmic immune receptor tyrosine-based inhibitory motifs, or ITIMs. SIGLECs are typically expressed on cells of the innate immune system, with the exception of the B-cell expressed SIGLEC6 (MIM 604405).[supplied by OMIM, Jul 2002]

SIGLEC10 links:

SIGLEC10-AS1 (HGNC:40719): (SIGLEC10 antisense RNA 1)

SIGLEC10-AS1 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.064695895).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SIGLEC10	NM_033130.5 link	c.397G>T	p.Asp133Tyr	missense_variant	Exon 2 of 11	ENST00000339313.10	NP_149121.2	Q96LC7-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SIGLEC10	ENST00000339313.10 link	c.397G>T	p.Asp133Tyr	missense_variant	Exon 2 of 11	1	NM_033130.5	ENSP00000345243.4		Q96LC7-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251282

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135842

show subpopulations

Gnomad AFR exome

AF:

0.00

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:

0.00000880

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461856

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727234

show subpopulations

Gnomad4 AFR exome

AF:

0.00

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:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.099

BayesDel_addAF

Benign

-0.033

BayesDel_noAF

Benign

-0.29

CADD

Benign

0.0030

DANN

Benign

0.54

DEOGEN2

Benign

0.098

.;.;.;.;.;.;T;T

Eigen

Benign

-2.3

Eigen_PC

Benign

-2.4

FATHMM_MKL

Benign

0.0083

LIST_S2

Benign

0.44

T;T;T;T;T;T;T;T

M_CAP

Benign

0.046

MetaRNN

Benign

0.065

T;T;T;T;T;T;T;T

MetaSVM

Benign

-0.48

MutationAssessor

Benign

0.20

N;N;N;.;N;N;N;.

PrimateAI

Benign

0.38

PROVEAN

Benign

-0.64

N;N;N;N;N;N;N;N

REVEL

Benign

0.23

Sift

Benign

0.22

T;T;T;T;T;T;T;T

Sift4G

Benign

0.18

T;T;T;T;T;T;T;.

Polyphen

0.0010

B;B;.;B;.;B;B;.

Vest4

0.070

MutPred

0.37

Gain of ubiquitination at K138 (P = 0.0671);Gain of ubiquitination at K138 (P = 0.0671);Gain of ubiquitination at K138 (P = 0.0671);Gain of ubiquitination at K138 (P = 0.0671);Gain of ubiquitination at K138 (P = 0.0671);Gain of ubiquitination at K138 (P = 0.0671);Gain of ubiquitination at K138 (P = 0.0671);.;

MVP

0.37

ClinPred

0.098

GERP RS

-9.3

Varity_R

0.040

gMVP

0.37

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.10

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over