rs10993726

Variant names:

• chr9-90858466-C-T
• rs10993726
• NM_003177.7:c.579-3740C>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.579-3740C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.199 in 152,244 control chromosomes in the GnomAD database, including 3,402 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 0.20 (3402 hom., cov: 33)
• Consequence: SYK NM_003177.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.938
• 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), PanelApp Australia

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.254 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.579-3740C>T		intron	N/A	NP_003168.2
	SYK	NM_001174167.3		c.579-3740C>T		intron	N/A	NP_001167638.1	P43405-1
	SYK	NM_001135052.4		c.579-3740C>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.579-3740C>T		intron	N/A	ENSP00000364907.4	P43405-1
	SYK	ENST00000375746.1	TSL:1	c.579-3740C>T		intron	N/A	ENSP00000364898.1	P43405-1
	SYK	ENST00000375747.5	TSL:1	c.579-3740C>T		intron	N/A	ENSP00000364899.1	P43405-2

Frequencies

GnomAD3 genomes AF: 0.199 AC: 30328 AN: 152126 Hom.: 3404 Cov.: 33

Gnomad AFR AF: 0.161

Gnomad AMI AF: 0.161

Gnomad AMR AF: 0.186

Gnomad ASJ AF: 0.250

Gnomad EAS AF: 0.00346

Gnomad SAS AF: 0.116

Gnomad FIN AF: 0.105

Gnomad MID AF: 0.329

Gnomad NFE AF: 0.257

Gnomad OTH AF: 0.238

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

GnomAD4 genome AF: 0.199 AC: 30319 AN: 152244 Hom.: 3402 Cov.: 33 AF XY: 0.191 AC XY: 14200 AN XY: 74440

African (AFR) AF: 0.161 AC: 6671 AN: 41546

American (AMR) AF: 0.186 AC: 2845 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.250 AC: 869 AN: 3470

East Asian (EAS) AF: 0.00347 AC: 18 AN: 5190

South Asian (SAS) AF: 0.115 AC: 555 AN: 4826

European-Finnish (FIN) AF: 0.105 AC: 1110 AN: 10606

Middle Eastern (MID) AF: 0.330 AC: 97 AN: 294

European-Non Finnish (NFE) AF: 0.257 AC: 17507 AN: 67990

Other (OTH) AF: 0.237 AC: 500 AN: 2114

Alfa AF: 0.226 Hom.: 2236

Bravo AF: 0.204

Asia WGS AF: 0.0620 AC: 218 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.1
DANN	Benign	0.72
PhyloP100		-0.94
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: rs10993726; hg19: chr9-93620748;