Genetic Variant NM_033130.5:c.449T>C (chr19-51416923-A-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_033130.5(SIGLEC10):c.449T>C(p.Ile150Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,276 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

SIGLEC10
NM_033130.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.57

Publications

0 publications found

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 was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.2334505).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_033130.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SIGLEC10	NM_033130.5	MANE Select	c.449T>C	p.Ile150Thr	missense	Exon 3 of 11	NP_149121.2
SIGLEC10	NM_001171157.2		c.449T>C	p.Ile150Thr	missense	Exon 3 of 10	NP_001164628.1	Q96LC7-2
SIGLEC10	NM_001322105.2		c.449T>C	p.Ile150Thr	missense	Exon 3 of 9	NP_001309034.1	E9PL79

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SIGLEC10	ENST00000339313.10	TSL:1 MANE Select	c.449T>C	p.Ile150Thr	missense	Exon 3 of 11	ENSP00000345243.4	Q96LC7-1
SIGLEC10	ENST00000353836.9	TSL:1	c.449T>C	p.Ile150Thr	missense	Exon 3 of 10	ENSP00000342389.5	Q96LC7-2
SIGLEC10	ENST00000439889.6	TSL:1	c.422-147T>C		intron	N/A	ENSP00000389132.2	Q96LC7-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461276

Hom.:

Cov.:

102

AF XY:

0.00000138

AC XY:

AN XY:

726930

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33464

American (AMR)

AF:

0.00

AC:

AN:

44702

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26076

East Asian (EAS)

AF:

0.00

AC:

AN:

39692

South Asian (SAS)

AF:

0.00

AC:

AN:

86212

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53384

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

0.00000180

AC:

AN:

1111612

Other (OTH)

AF:

0.00

AC:

AN:

60370

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000470

Hom.:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

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

Pathogenic

0.62

BayesDel_addAF

Benign

-0.061

BayesDel_noAF

Benign

-0.33

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.44

Eigen

Benign

-0.23

Eigen_PC

Benign

-0.30

FATHMM_MKL

Benign

0.22

LIST_S2

Benign

0.33

M_CAP

Benign

0.056

MetaRNN

Benign

0.23

MetaSVM

Benign

-0.56

MutationAssessor

Pathogenic

2.9

PhyloP100

1.6

PrimateAI

Benign

0.41

PROVEAN

Uncertain

-3.3

REVEL

Uncertain

0.31

Sift

Uncertain

0.022

Sift4G

Uncertain

0.0030

Polyphen

0.20

Vest4

0.22

MutPred

0.46

Gain of disorder (P = 0.009)

MVP

0.70

ClinPred

0.90

GERP RS

4.7

Varity_R

0.11

gMVP

0.33

Mutation Taster

=78/22

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over