Variant 9-90874733-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1

The NM_003177.7(SYK):c.1065C>T(p.Pro355Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.157 in 1,613,792 control chromosomes in the GnomAD database, including 22,523 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.18 ( 2934 hom., cov: 32)

Exomes 𝑓: 0.15 ( 19589 hom. )

Consequence

SYK
NM_003177.7 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -5.12

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.68).

BP6

Variant 9-90874733-C-T is Benign according to our data. Variant chr9-90874733-C-T is described in ClinVar as [Benign]. Clinvar id is 2688051.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-5.12 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.294 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SYK	NM_003177.7 linkuse as main transcript	c.1065C>T	p.Pro355Pro	synonymous_variant	9/14	ENST00000375754.9	NP_003168.2	P43405-1A0A024R244

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
SYK	ENST00000375754.9 linkuse as main transcript	c.1065C>T	p.Pro355Pro	synonymous_variant	9/14	1	NM_003177.7	ENSP00000364907.4	P43405-1
SYK	ENST00000375746.1 linkuse as main transcript	c.1065C>T	p.Pro355Pro	synonymous_variant	9/14	1		ENSP00000364898.1	P43405-1
SYK	ENST00000375747.5 linkuse as main transcript	c.996C>T	p.Pro332Pro	synonymous_variant	8/13	1		ENSP00000364899.1	P43405-2
SYK	ENST00000375751.8 linkuse as main transcript	c.996C>T	p.Pro332Pro	synonymous_variant	8/13	1		ENSP00000364904.4	P43405-2

Frequencies

GnomAD3 genomes

AF:

0.184

AC:

27989

AN:

151830

Hom.:

2922

Cov.:

show subpopulations

Gnomad AFR

AF:

0.208

Gnomad AMI

AF:

0.345

Gnomad AMR

AF:

0.301

Gnomad ASJ

AF:

0.202

Gnomad EAS

AF:

0.233

Gnomad SAS

AF:

0.100

Gnomad FIN

AF:

0.191

Gnomad MID

AF:

0.196

Gnomad NFE

AF:

0.142

Gnomad OTH

AF:

0.182

GnomAD3 exomes

AF:

0.194

AC:

48818

AN:

251438

Hom.:

6144

AF XY:

0.181

AC XY:

24542

AN XY:

135894

show subpopulations

Gnomad AFR exome

AF:

0.206

Gnomad AMR exome

AF:

0.416

Gnomad ASJ exome

AF:

0.202

Gnomad EAS exome

AF:

0.234

Gnomad SAS exome

AF:

0.104

Gnomad FIN exome

AF:

0.198

Gnomad NFE exome

AF:

0.143

Gnomad OTH exome

AF:

0.174

GnomAD4 exome

AF:

0.154

AC:

225468

AN:

1461842

Hom.:

19589

Cov.:

AF XY:

0.151

AC XY:

110139

AN XY:

727228

show subpopulations

Gnomad4 AFR exome

AF:

0.208

Gnomad4 AMR exome

AF:

0.405

Gnomad4 ASJ exome

AF:

0.204

Gnomad4 EAS exome

AF:

0.201

Gnomad4 SAS exome

AF:

0.109

Gnomad4 FIN exome

AF:

0.198

Gnomad4 NFE exome

AF:

0.141

Gnomad4 OTH exome

AF:

0.160

GnomAD4 genome

AF:

0.184

AC:

28027

AN:

151950

Hom.:

2934

Cov.:

AF XY:

0.186

AC XY:

13845

AN XY:

74262

show subpopulations

Gnomad4 AFR

AF:

0.208

Gnomad4 AMR

AF:

0.302

Gnomad4 ASJ

AF:

0.202

Gnomad4 EAS

AF:

0.234

Gnomad4 SAS

AF:

0.101

Gnomad4 FIN

AF:

0.191

Gnomad4 NFE

AF:

0.142

Gnomad4 OTH

AF:

0.182

Alfa

AF:

0.152

Hom.:

4524

Bravo

AF:

0.196

Asia WGS

AF:

0.170

AC:

589

AN:

3478

EpiCase

AF:

0.139

EpiControl

AF:

0.137

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Jan 24, 2024

This variant is classified as Benign based on local population frequency. This variant was detected in 63% of patients studied by a panel of primary immunodeficiencies. Number of patients: 60. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.68

CADD

Benign

0.19

DANN

Benign

0.77

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