9-90865202-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.443

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]

ACMG classification

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	c.846+105C>T		intron_variant		ENST00000375754.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SYK	ENST00000375754.9	c.846+105C>T		intron_variant		1	NM_003177.7	P1
SYK	ENST00000375746.1	c.846+105C>T		intron_variant		1		P1
SYK	ENST00000375747.5	c.846+105C>T		intron_variant		1
SYK	ENST00000375751.8	c.846+105C>T		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.433 AC: 65865 AN: 152016 Hom.: 14683 Cov.: 33

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

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.: 33 AF XY: 0.426 AC XY: 31657 AN XY: 74358

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

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

Other links and lift over

dbSNP: rs4744516; hg19: chr9-93627484; COSMIC: COSV65326864;