Genetic Variant SYK:p.Tyr352Tyr (chr9-90874724-C-T) – ACMG Classification: Benign (-11 pts)

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_003177.7(SYK):c.1056C>T(p.Tyr352Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00553 in 1,614,096 control chromosomes in the GnomAD database, including 44 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0045 ( 6 hom., cov: 32)

Exomes 𝑓: 0.0056 ( 38 hom. )

Consequence

SYK
NM_003177.7 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.66

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.52).

BP6

Variant 9-90874724-C-T is Benign according to our data. Variant chr9-90874724-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3341527.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-1.66 with no splicing effect.

BS2

High AC in GnomAd4 at 684 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SYK	NM_003177.7 link	c.1056C>T	p.Tyr352Tyr	synonymous_variant	Exon 9 of 14	ENST00000375754.9	NP_003168.2	P43405-1A0A024R244

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
SYK	ENST00000375754.9 link	c.1056C>T	p.Tyr352Tyr	synonymous_variant	Exon 9 of 14	1	NM_003177.7	ENSP00000364907.4	P43405-1
SYK	ENST00000375746.1 link	c.1056C>T	p.Tyr352Tyr	synonymous_variant	Exon 9 of 14	1		ENSP00000364898.1	P43405-1
SYK	ENST00000375747.5 link	c.987C>T	p.Tyr329Tyr	synonymous_variant	Exon 8 of 13	1		ENSP00000364899.1	P43405-2
SYK	ENST00000375751.8 link	c.987C>T	p.Tyr329Tyr	synonymous_variant	Exon 8 of 13	1		ENSP00000364904.4	P43405-2

Frequencies

GnomAD3 genomes

AF:

0.00450

AC:

684

AN:

152122

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00126

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00445

Gnomad ASJ

AF:

0.0101

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00145

Gnomad FIN

AF:

0.000566

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00744

Gnomad OTH

AF:

0.00479

GnomAD3 exomes

AF:

0.00430

AC:

1082

AN:

251448

Hom.:

AF XY:

0.00422

AC XY:

573

AN XY:

135900

show subpopulations

Gnomad AFR exome

AF:

0.00135

Gnomad AMR exome

AF:

0.00298

Gnomad ASJ exome

AF:

0.00903

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00131

Gnomad FIN exome

AF:

0.00134

Gnomad NFE exome

AF:

0.00671

Gnomad OTH exome

AF:

0.00537

GnomAD4 exome

AF:

0.00564

AC:

8243

AN:

1461856

Hom.:

Cov.:

AF XY:

0.00554

AC XY:

4026

AN XY:

727228

show subpopulations

Gnomad4 AFR exome

AF:

0.00108

Gnomad4 AMR exome

AF:

0.00347

Gnomad4 ASJ exome

AF:

0.0103

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.00187

Gnomad4 FIN exome

AF:

0.00168

Gnomad4 NFE exome

AF:

0.00653

Gnomad4 OTH exome

AF:

0.00434

GnomAD4 genome

AF:

0.00449

AC:

684

AN:

152240

Hom.:

Cov.:

AF XY:

0.00381

AC XY:

284

AN XY:

74446

show subpopulations

Gnomad4 AFR

AF:

0.00125

Gnomad4 AMR

AF:

0.00444

Gnomad4 ASJ

AF:

0.0101

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00145

Gnomad4 FIN

AF:

0.000566

Gnomad4 NFE

AF:

0.00744

Gnomad4 OTH

AF:

0.00474

Alfa

AF:

0.00673

Hom.:

Bravo

AF:

0.00495

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00682

EpiControl

AF:

0.00688

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Feb 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

SYK: BP4, BP7, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.52

CADD

Benign

0.76

DANN

Benign

0.55

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

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over