Genetic Variant NM_033130.5:c.944C>G (chr19-51415978-G-C) – 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.944C>G(p.Ala315Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,134 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. A315D) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Consequence

SIGLEC10
NM_033130.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.32

Publications

2 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=0.18694782).

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.944C>G	p.Ala315Gly	missense	Exon 5 of 11	NP_149121.2
SIGLEC10	NM_001171156.2		c.770C>G	p.Ala257Gly	missense	Exon 5 of 11	NP_001164627.1	Q96LC7-3
SIGLEC10	NM_001171157.2		c.944C>G	p.Ala315Gly	missense	Exon 5 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.944C>G	p.Ala315Gly	missense	Exon 5 of 11	ENSP00000345243.4	Q96LC7-1
SIGLEC10	ENST00000439889.6	TSL:1	c.770C>G	p.Ala257Gly	missense	Exon 5 of 11	ENSP00000389132.2	Q96LC7-3
SIGLEC10	ENST00000353836.9	TSL:1	c.944C>G	p.Ala315Gly	missense	Exon 5 of 10	ENSP00000342389.5	Q96LC7-2

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152134

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152134

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74304

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41452

American (AMR)

AF:

0.00

AC:

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5166

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68004

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.54

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.11

Eigen

Benign

-0.36

Eigen_PC

Benign

-0.58

FATHMM_MKL

Benign

0.030

LIST_S2

Benign

0.57

M_CAP

Benign

0.011

MetaRNN

Benign

0.19

MetaSVM

Benign

-0.96

MutationAssessor

Benign

2.0

PhyloP100

1.3

PrimateAI

Benign

0.34

PROVEAN

Uncertain

-2.4

REVEL

Benign

0.047

Sift

Benign

0.071

Sift4G

Benign

0.30

Polyphen

0.94

Vest4

0.12

MutPred

0.40

Loss of sheet (P = 0.0817)

MVP

0.53

ClinPred

0.39

GERP RS

0.71

Varity_R

0.14

gMVP

0.21

Mutation Taster

=90/10

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