9-90843821-G-A

Position:

• chr9-90843821-G-A

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.-41-37G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.266 in 1,382,802 control chromosomes in the GnomAD database, including 52,035 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.31 (7874 hom., cov: 32)
  • Exomes 𝑓: 0.26 (44161 hom.)
• Consequence: SYK NM_003177.7 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.834

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 9-90843821-G-A is Benign according to our data. Variant chr9-90843821-G-A is described in ClinVar as [Benign]. Clinvar id is 2688069.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.413 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SYK	NM_003177.7	c.-41-37G>A		intron_variant		ENST00000375754.9	NP_003168.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SYK	ENST00000375754.9	c.-41-37G>A		intron_variant		1	NM_003177.7	ENSP00000364907.4

Frequencies

GnomAD3 genomes AF: 0.306 AC: 46427 AN: 151888 Hom.: 7865 Cov.: 32

Gnomad AFR AF: 0.419

Gnomad AMI AF: 0.455

Gnomad AMR AF: 0.365

Gnomad ASJ AF: 0.295

Gnomad EAS AF: 0.0323

Gnomad SAS AF: 0.225

Gnomad FIN AF: 0.155

Gnomad MID AF: 0.370

Gnomad NFE AF: 0.272

Gnomad OTH AF: 0.309

GnomAD4 exome AF: 0.261 AC: 321420 AN: 1230794 Hom.: 44161 Cov.: 23 AF XY: 0.261 AC XY: 155011 AN XY: 594188

Gnomad4 AFR exome AF: 0.432

Gnomad4 AMR exome AF: 0.376

Gnomad4 ASJ exome AF: 0.296

Gnomad4 EAS exome AF: 0.0234

Gnomad4 SAS exome AF: 0.223

Gnomad4 FIN exome AF: 0.170

Gnomad4 NFE exome AF: 0.266

Gnomad4 OTH exome AF: 0.263

GnomAD4 genome AF: 0.306 AC: 46464 AN: 152008 Hom.: 7874 Cov.: 32 AF XY: 0.299 AC XY: 22225 AN XY: 74314

Gnomad4 AFR AF: 0.418

Gnomad4 AMR AF: 0.365

Gnomad4 ASJ AF: 0.295

Gnomad4 EAS AF: 0.0322

Gnomad4 SAS AF: 0.225

Gnomad4 FIN AF: 0.155

Gnomad4 NFE AF: 0.272

Gnomad4 OTH AF: 0.308

Alfa AF: 0.274 Hom.: 7935

Bravo AF: 0.327

Asia WGS AF: 0.167 AC: 581 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 61% of patients studied by a panel of primary immunodeficiencies. Number of patients: 58. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.0
DANN	Benign	0.62

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: rs7855964; hg19: chr9-93606103;