Genetic Variant SYK:c.-42+10475C>T (chr9-90812368-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_003177.7(SYK):c.-42+10475C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.778 in 152,054 control chromosomes in the GnomAD database, including 46,484 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.78 ( 46484 hom., cov: 30)

Consequence

SYK
NM_003177.7 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.64

Publications

4 publications found

Variant links:

Genes affected

SYK (HGNC:11491): (spleen associated tyrosine kinase) This gene encodes a member of the family of non-receptor type Tyr protein kinases. This protein is widely expressed in hematopoietic cells and is involved in coupling activated immunoreceptors to downstream signaling events that mediate diverse cellular responses, including proliferation, differentiation, and phagocytosis. It is thought to be a modulator of epithelial cell growth and a potential tumour suppressor in human breast carcinomas. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Mar 2010]

SYK Gene-Disease associations (from GenCC):

immunodeficiency 82 with systemic inflammation
Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), PanelApp Australia

SYK links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.94).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.971 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003177.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SYK	NM_003177.7	MANE Select	c.-42+10475C>T	intron	N/A	NP_003168.2
SYK	NM_001135052.4		c.-42+10475C>T	intron	N/A	NP_001128524.1	P43405-2
SYK	NM_001174168.3		c.-42+10363C>T	intron	N/A	NP_001167639.1	P43405-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SYK	ENST00000375754.9	TSL:1 MANE Select	c.-42+10475C>T	intron	N/A	ENSP00000364907.4	P43405-1
SYK	ENST00000375747.5	TSL:1	c.-42+10363C>T	intron	N/A	ENSP00000364899.1	P43405-2
SYK	ENST00000375751.8	TSL:1	c.-42+10475C>T	intron	N/A	ENSP00000364904.4	P43405-2

Frequencies

GnomAD3 genomes

AF:

0.778

AC:

118230

AN:

151936

Hom.:

46432

Cov.:

show subpopulations

Gnomad AFR

AF:

0.685

Gnomad AMI

AF:

0.633

Gnomad AMR

AF:

0.844

Gnomad ASJ

AF:

0.754

Gnomad EAS

AF:

0.993

Gnomad SAS

AF:

0.823

Gnomad FIN

AF:

0.838

Gnomad MID

AF:

0.753

Gnomad NFE

AF:

0.794

Gnomad OTH

AF:

0.803

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.778

AC:

118343

AN:

152054

Hom.:

46484

Cov.:

AF XY:

0.783

AC XY:

58231

AN XY:

74330

show subpopulations

African (AFR)

AF:

0.685

AC:

28405

AN:

41448

American (AMR)

AF:

0.844

AC:

12915

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.754

AC:

2617

AN:

3470

East Asian (EAS)

AF:

0.993

AC:

5144

AN:

5178

South Asian (SAS)

AF:

0.824

AC:

3962

AN:

4808

European-Finnish (FIN)

AF:

0.838

AC:

8871

AN:

10580

Middle Eastern (MID)

AF:

0.745

AC:

219

AN:

294

European-Non Finnish (NFE)

AF:

0.794

AC:

53937

AN:

67964

Other (OTH)

AF:

0.805

AC:

1697

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1313

2626

3939

5252

6565

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

866

1732

2598

3464

4330

<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:

0.787

Hom.:

135413

Bravo

AF:

0.775

Asia WGS

AF:

0.901

AC:

3133

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.94

CADD

Benign

0.12

(source)

DANN

Benign

0.38

PhyloP100

-1.6

Mutation Taster

=100/0

polymorphism (auto)

(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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over