9-90858466-C-T

Position:

• chr9-90858466-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003177.7(SYK):​c.579-3740C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.199 in 152,244 control chromosomes in the GnomAD database, including 3,402 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.20 (3402 hom., cov: 33)
• Consequence: SYK NM_003177.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.938

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.254 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SYK	NM_003177.7	c.579-3740C>T		intron_variant		ENST00000375754.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SYK	ENST00000375754.9	c.579-3740C>T		intron_variant		1	NM_003177.7	P1
SYK	ENST00000375746.1	c.579-3740C>T		intron_variant		1		P1
SYK	ENST00000375747.5	c.579-3740C>T		intron_variant		1
SYK	ENST00000375751.8	c.579-3740C>T		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.199 AC: 30328 AN: 152126 Hom.: 3404 Cov.: 33

Gnomad AFR AF: 0.161

Gnomad AMI AF: 0.161

Gnomad AMR AF: 0.186

Gnomad ASJ AF: 0.250

Gnomad EAS AF: 0.00346

Gnomad SAS AF: 0.116

Gnomad FIN AF: 0.105

Gnomad MID AF: 0.329

Gnomad NFE AF: 0.257

Gnomad OTH AF: 0.238

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.199 AC: 30319 AN: 152244 Hom.: 3402 Cov.: 33 AF XY: 0.191 AC XY: 14200 AN XY: 74440

Gnomad4 AFR AF: 0.161

Gnomad4 AMR AF: 0.186

Gnomad4 ASJ AF: 0.250

Gnomad4 EAS AF: 0.00347

Gnomad4 SAS AF: 0.115

Gnomad4 FIN AF: 0.105

Gnomad4 NFE AF: 0.257

Gnomad4 OTH AF: 0.237

Alfa AF: 0.225 Hom.: 1432

Bravo AF: 0.204

Asia WGS AF: 0.0620 AC: 218 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.1
DANN	Benign	0.72

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: rs10993726; hg19: chr9-93620748;