Variant chr9-90865202-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_003177.7(SYK):c.846+105C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.417 in 1,151,070 control chromosomes in the GnomAD database, including 103,781 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.43 ( 14690 hom., cov: 33)

Exomes 𝑓: 0.41 ( 89091 hom. )

Consequence

SYK
NM_003177.7 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.443

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 9-90865202-C-T is Benign according to our data. Variant chr9-90865202-C-T is described in ClinVar as [Benign]. Clinvar id is 2688027.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.523 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SYK	NM_003177.7 linkuse as main transcript	c.846+105C>T		intron_variant		ENST00000375754.9

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Appris	UniProt
SYK	ENST00000375754.9 linkuse as main transcript	c.846+105C>T	intron_variant	1	NM_003177.7	P1	P43405-1
SYK	ENST00000375746.1 linkuse as main transcript	c.846+105C>T	intron_variant	1		P1	P43405-1
SYK	ENST00000375747.5 linkuse as main transcript	c.846+105C>T	intron_variant	1			P43405-2
SYK	ENST00000375751.8 linkuse as main transcript	c.846+105C>T	intron_variant	1			P43405-2

Frequencies

GnomAD3 genomes

AF:

0.433

AC:

65865

AN:

152016

Hom.:

14683

Cov.:

show subpopulations

Gnomad AFR

AF:

0.455

Gnomad AMI

AF:

0.540

Gnomad AMR

AF:

0.533

Gnomad ASJ

AF:

0.495

Gnomad EAS

AF:

0.214

Gnomad SAS

AF:

0.228

Gnomad FIN

AF:

0.337

Gnomad MID

AF:

0.560

Gnomad NFE

AF:

0.437

Gnomad OTH

AF:

0.476

GnomAD4 exome

AF:

0.414

AC:

413889

AN:

998938

Hom.:

89091

AF XY:

0.408

AC XY:

209752

AN XY:

514482

show subpopulations

Gnomad4 AFR exome

AF:

0.454

Gnomad4 AMR exome

AF:

0.573

Gnomad4 ASJ exome

AF:

0.496

Gnomad4 EAS exome

AF:

0.191

Gnomad4 SAS exome

AF:

0.241

Gnomad4 FIN exome

AF:

0.355

Gnomad4 NFE exome

AF:

0.435

Gnomad4 OTH exome

AF:

0.416

GnomAD4 genome

AF:

0.433

AC:

65908

AN:

152132

Hom.:

14690

Cov.:

AF XY:

0.426

AC XY:

31657

AN XY:

74358

show subpopulations

Gnomad4 AFR

AF:

0.455

Gnomad4 AMR

AF:

0.533

Gnomad4 ASJ

AF:

0.495

Gnomad4 EAS

AF:

0.215

Gnomad4 SAS

AF:

0.227

Gnomad4 FIN

AF:

0.337

Gnomad4 NFE

AF:

0.437

Gnomad4 OTH

AF:

0.474

Alfa

AF:

0.433

Hom.:

19033

Bravo

AF:

0.452

Asia WGS

AF:

0.234

AC:

815

AN:

3478

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 68% of patients studied by a panel of primary immunodeficiencies. Number of patients: 65. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

5.9

DANN

Benign

0.76

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