9-90868163-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.915+964C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.845 in 152,232 control chromosomes in the GnomAD database, including 54,697 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 0.84 (54697 hom., cov: 33)
• Consequence: SYK NM_003177.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.22

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=-1.01).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.933 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SYK	NM_003177.7	c.915+964C>T		intron_variant		ENST00000375754.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SYK	ENST00000375754.9	c.915+964C>T		intron_variant		1	NM_003177.7	P1
SYK	ENST00000375746.1	c.915+964C>T		intron_variant		1		P1
SYK	ENST00000375747.5	c.846+3066C>T		intron_variant		1
SYK	ENST00000375751.8	c.846+3066C>T		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.844 AC: 128455 AN: 152114 Hom.: 54643 Cov.: 33

Gnomad AFR AF: 0.931

Gnomad AMI AF: 0.932

Gnomad AMR AF: 0.863

Gnomad ASJ AF: 0.858

Gnomad EAS AF: 0.955

Gnomad SAS AF: 0.856

Gnomad FIN AF: 0.810

Gnomad MID AF: 0.930

Gnomad NFE AF: 0.781

Gnomad OTH AF: 0.856

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

GnomAD4 genome AF: 0.845 AC: 128568 AN: 152232 Hom.: 54697 Cov.: 33 AF XY: 0.848 AC XY: 63130 AN XY: 74428

Gnomad4 AFR AF: 0.932

Gnomad4 AMR AF: 0.863

Gnomad4 ASJ AF: 0.858

Gnomad4 EAS AF: 0.955

Gnomad4 SAS AF: 0.855

Gnomad4 FIN AF: 0.810

Gnomad4 NFE AF: 0.781

Gnomad4 OTH AF: 0.857

Alfa AF: 0.791 Hom.: 26646

Bravo AF: 0.854

Asia WGS AF: 0.917 AC: 3186 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	0.039
Dann	Benign	0.59

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: rs2613310; hg19: chr9-93630445;