Genetic Variant NM_033130.5:c.1684C>A (chr19-51414447-G-T) – 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.1684C>A(p.Leu562Ile) 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 1,461,710 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L562F) has been classified as Uncertain significance.

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: 0.625

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-AS2 (HGNC:40718): (SIGLEC10 antisense RNA 2)

SIGLEC10-AS2 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=0.24813524).

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.1684C>A	p.Leu562Ile	missense	Exon 9 of 11	NP_149121.2
SIGLEC10	NM_001171156.2		c.1510C>A	p.Leu504Ile	missense	Exon 9 of 11	NP_001164627.1	Q96LC7-3
SIGLEC10	NM_001171157.2		c.1399C>A	p.Leu467Ile	missense	Exon 8 of 10	NP_001164628.1	Q96LC7-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SIGLEC10	ENST00000339313.10	TSL:1 MANE Select	c.1684C>A	p.Leu562Ile	missense	Exon 9 of 11	ENSP00000345243.4	Q96LC7-1
SIGLEC10	ENST00000439889.6	TSL:1	c.1510C>A	p.Leu504Ile	missense	Exon 9 of 11	ENSP00000389132.2	Q96LC7-3
SIGLEC10	ENST00000353836.9	TSL:1	c.1399C>A	p.Leu467Ile	missense	Exon 8 of 10	ENSP00000342389.5	Q96LC7-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461710

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727134

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33478

American (AMR)

AF:

0.00

AC:

AN:

44702

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26124

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86190

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53408

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

8.99e-7

AC:

AN:

1111948

Other (OTH)

AF:

0.00

AC:

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

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

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.062

BayesDel_noAF

Benign

-0.33

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.22

Eigen

Benign

0.040

Eigen_PC

Benign

-0.16

FATHMM_MKL

Benign

0.27

LIST_S2

Benign

0.72

M_CAP

Benign

0.011

MetaRNN

Benign

0.25

MetaSVM

Benign

-0.78

MutationAssessor

Pathogenic

2.9

PhyloP100

0.63

PrimateAI

Benign

0.33

PROVEAN

Benign

-1.4

REVEL

Benign

0.11

Sift

Benign

0.045

Sift4G

Uncertain

0.038

Polyphen

1.0

Vest4

0.26

MutPred

0.34

Loss of sheet (P = 0.0457)

MVP

0.55

ClinPred

0.88

GERP RS

2.6

Varity_R

0.11

gMVP

0.25

Mutation Taster

=91/9

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over