9-90833525-C-T

Position:

• chr9-90833525-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.-41-10333C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.861 in 152,218 control chromosomes in the GnomAD database, including 56,706 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 0.86 (56706 hom., cov: 32)
• Consequence: SYK NM_003177.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.746

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.976 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SYK	NM_003177.7	c.-41-10333C>T		intron_variant		ENST00000375754.9	NP_003168.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SYK	ENST00000375754.9	c.-41-10333C>T		intron_variant		1	NM_003177.7	ENSP00000364907.4

Frequencies

GnomAD3 genomes AF: 0.861 AC: 131009 AN: 152100 Hom.: 56651 Cov.: 32

Gnomad AFR AF: 0.916

Gnomad AMI AF: 0.882

Gnomad AMR AF: 0.892

Gnomad ASJ AF: 0.815

Gnomad EAS AF: 0.998

Gnomad SAS AF: 0.891

Gnomad FIN AF: 0.845

Gnomad MID AF: 0.820

Gnomad NFE AF: 0.814

Gnomad OTH AF: 0.852

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

GnomAD4 genome AF: 0.861 AC: 131123 AN: 152218 Hom.: 56706 Cov.: 32 AF XY: 0.864 AC XY: 64340 AN XY: 74428

Gnomad4 AFR AF: 0.916

Gnomad4 AMR AF: 0.892

Gnomad4 ASJ AF: 0.815

Gnomad4 EAS AF: 0.998

Gnomad4 SAS AF: 0.892

Gnomad4 FIN AF: 0.845

Gnomad4 NFE AF: 0.814

Gnomad4 OTH AF: 0.852

Alfa AF: 0.824 Hom.: 71966

Bravo AF: 0.868

Asia WGS AF: 0.946 AC: 3292 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.76
DANN	Benign	0.32

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: rs290213; hg19: chr9-93595807;