9-90833525-C-T

Variant names:

• chr9-90833525-C-T
• rs290213
• NM_003177.7:c.-41-10333C>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.-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
• Publications: 8 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), PanelApp Australia

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 = 0.976 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003177.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SYK	NM_003177.7	MANE Select	c.-41-10333C>T		intron	N/A	NP_003168.2
	SYK	NM_001174167.3		c.-42+5946C>T		intron	N/A	NP_001167638.1	P43405-1
	SYK	NM_001135052.4		c.-41-10333C>T		intron	N/A	NP_001128524.1	P43405-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SYK	ENST00000375754.9	TSL:1 MANE Select	c.-41-10333C>T		intron	N/A	ENSP00000364907.4	P43405-1
	SYK	ENST00000375746.1	TSL:1	c.-42+5946C>T		intron	N/A	ENSP00000364898.1	P43405-1
	SYK	ENST00000375747.5	TSL:1	c.-41-10333C>T		intron	N/A	ENSP00000364899.1	P43405-2

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

African (AFR) AF: 0.916 AC: 38048 AN: 41538

American (AMR) AF: 0.892 AC: 13639 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.815 AC: 2826 AN: 3468

East Asian (EAS) AF: 0.998 AC: 5171 AN: 5180

South Asian (SAS) AF: 0.892 AC: 4299 AN: 4820

European-Finnish (FIN) AF: 0.845 AC: 8950 AN: 10596

Middle Eastern (MID) AF: 0.823 AC: 242 AN: 294

European-Non Finnish (NFE) AF: 0.814 AC: 55345 AN: 68008

Other (OTH) AF: 0.852 AC: 1800 AN: 2112

Alfa AF: 0.828 Hom.: 100155

Bravo AF: 0.868

Asia WGS AF: 0.946 AC: 3292 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.76
DANN	Benign	0.32
PhyloP100		-0.75
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: rs290213; hg19: chr9-93595807;