9-90812368-C-T

Variant names:

• chr9-90812368-C-T
• rs290237
• NM_003177.7:c.-42+10475C>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.-42+10475C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.778 in 152,054 control chromosomes in the GnomAD database, including 46,484 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 0.78 (46484 hom., cov: 30)
• Consequence: SYK NM_003177.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.64
• Publications: 4 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=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.971 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SYK	NM_003177.7	c.-42+10475C>T		intron_variant	Intron 1 of 13	ENST00000375754.9	NP_003168.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SYK	ENST00000375754.9	c.-42+10475C>T		intron_variant	Intron 1 of 13	1	NM_003177.7	ENSP00000364907.4
SYK	ENST00000375747.5	c.-42+10363C>T		intron_variant	Intron 1 of 12	1		ENSP00000364899.1
SYK	ENST00000375751.8	c.-42+10475C>T		intron_variant	Intron 1 of 12	1		ENSP00000364904.4
SYK	ENST00000476708.1	n.78+10329C>T		intron_variant	Intron 1 of 1	2

Frequencies

GnomAD3 genomes AF: 0.778 AC: 118230 AN: 151936 Hom.: 46432 Cov.: 30

Gnomad AFR AF: 0.685

Gnomad AMI AF: 0.633

Gnomad AMR AF: 0.844

Gnomad ASJ AF: 0.754

Gnomad EAS AF: 0.993

Gnomad SAS AF: 0.823

Gnomad FIN AF: 0.838

Gnomad MID AF: 0.753

Gnomad NFE AF: 0.794

Gnomad OTH AF: 0.803

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

GnomAD4 genome AF: 0.778 AC: 118343 AN: 152054 Hom.: 46484 Cov.: 30 AF XY: 0.783 AC XY: 58231 AN XY: 74330

African (AFR) AF: 0.685 AC: 28405 AN: 41448

American (AMR) AF: 0.844 AC: 12915 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.754 AC: 2617 AN: 3470

East Asian (EAS) AF: 0.993 AC: 5144 AN: 5178

South Asian (SAS) AF: 0.824 AC: 3962 AN: 4808

European-Finnish (FIN) AF: 0.838 AC: 8871 AN: 10580

Middle Eastern (MID) AF: 0.745 AC: 219 AN: 294

European-Non Finnish (NFE) AF: 0.794 AC: 53937 AN: 67964

Other (OTH) AF: 0.805 AC: 1697 AN: 2108

Alfa AF: 0.787 Hom.: 135413

Bravo AF: 0.775

Asia WGS AF: 0.901 AC: 3133 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	0.12
DANN	Benign	0.38
PhyloP100		-1.6
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: rs290237; hg19: chr9-93574650;