9-90868163-C-T

Variant names:

• chr9-90868163-C-T
• rs2613310
• NM_003177.7:c.915+964C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 10 publications found

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 Gene-Disease associations (from GenCC):

• immunodeficiency 82 with systemic inflammation

  Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
SYK	NM_003177.7	c.915+964C>T		intron_variant	Intron 7 of 13	ENST00000375754.9	NP_003168.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SYK	ENST00000375754.9	c.915+964C>T		intron_variant	Intron 7 of 13	1	NM_003177.7	ENSP00000364907.4
SYK	ENST00000375746.1	c.915+964C>T		intron_variant	Intron 7 of 13	1		ENSP00000364898.1
SYK	ENST00000375747.5	c.846+3066C>T		intron_variant	Intron 6 of 12	1		ENSP00000364899.1
SYK	ENST00000375751.8	c.846+3066C>T		intron_variant	Intron 6 of 12	1		ENSP00000364904.4

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

African (AFR) AF: 0.932 AC: 38717 AN: 41562

American (AMR) AF: 0.863 AC: 13204 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.858 AC: 2977 AN: 3470

East Asian (EAS) AF: 0.955 AC: 4954 AN: 5188

South Asian (SAS) AF: 0.855 AC: 4120 AN: 4816

European-Finnish (FIN) AF: 0.810 AC: 8575 AN: 10582

Middle Eastern (MID) AF: 0.922 AC: 271 AN: 294

European-Non Finnish (NFE) AF: 0.781 AC: 53094 AN: 68004

Other (OTH) AF: 0.857 AC: 1806 AN: 2108

Alfa AF: 0.799 Hom.: 37952

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
PhyloP100		-3.2
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2613310; hg19: chr9-93630445;