rs9695993

Variant names:

• chr9-90861482-A-C
• rs9695993
• NM_003177.7:c.579-724A>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003177.7(SYK):​c.579-724A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.154 in 151,376 control chromosomes in the GnomAD database, including 2,003 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 0.15 (2003 hom., cov: 31)
• Consequence: SYK NM_003177.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.238
• Publications: 7 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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.217 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SYK	NM_003177.7	c.579-724A>C		intron_variant	Intron 3 of 13	ENST00000375754.9	NP_003168.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SYK	ENST00000375754.9	c.579-724A>C		intron_variant	Intron 3 of 13	1	NM_003177.7	ENSP00000364907.4
SYK	ENST00000375746.1	c.579-724A>C		intron_variant	Intron 3 of 13	1		ENSP00000364898.1
SYK	ENST00000375747.5	c.579-724A>C		intron_variant	Intron 3 of 12	1		ENSP00000364899.1
SYK	ENST00000375751.8	c.579-724A>C		intron_variant	Intron 3 of 12	1		ENSP00000364904.4

Frequencies

GnomAD3 genomes AF: 0.154 AC: 23361 AN: 151260 Hom.: 2008 Cov.: 31

Gnomad AFR AF: 0.221

Gnomad AMI AF: 0.167

Gnomad AMR AF: 0.137

Gnomad ASJ AF: 0.127

Gnomad EAS AF: 0.133

Gnomad SAS AF: 0.205

Gnomad FIN AF: 0.0927

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.127

Gnomad OTH AF: 0.151

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

GnomAD4 genome AF: 0.154 AC: 23378 AN: 151376 Hom.: 2003 Cov.: 31 AF XY: 0.155 AC XY: 11466 AN XY: 73958

African (AFR) AF: 0.221 AC: 9080 AN: 41134

American (AMR) AF: 0.138 AC: 2095 AN: 15232

Ashkenazi Jewish (ASJ) AF: 0.127 AC: 442 AN: 3468

East Asian (EAS) AF: 0.133 AC: 680 AN: 5112

South Asian (SAS) AF: 0.204 AC: 974 AN: 4776

European-Finnish (FIN) AF: 0.0927 AC: 977 AN: 10542

Middle Eastern (MID) AF: 0.133 AC: 39 AN: 294

European-Non Finnish (NFE) AF: 0.127 AC: 8627 AN: 67834

Other (OTH) AF: 0.150 AC: 316 AN: 2100

Alfa AF: 0.141 Hom.: 838

Bravo AF: 0.160

Asia WGS AF: 0.187 AC: 634 AN: 3380

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.4
DANN	Benign	0.55
PhyloP100		-0.24
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: rs9695993; hg19: chr9-93623764;