rs3789889

Variant names:

• chr9-90809059-A-G
• rs3789889
• NM_003177.7:c.-42+7166A>G

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+7166A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.356 in 152,136 control chromosomes in the GnomAD database, including 9,795 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 0.36 (9795 hom., cov: 32)
• Consequence: SYK NM_003177.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.311
• Publications: 9 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 (AMR) allele frequency at 95% confidence interval = 0.447 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SYK	NM_003177.7	c.-42+7166A>G		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+7166A>G		intron_variant	Intron 1 of 13	1	NM_003177.7	ENSP00000364907.4
SYK	ENST00000375747.5	c.-42+7054A>G		intron_variant	Intron 1 of 12	1		ENSP00000364899.1
SYK	ENST00000375751.8	c.-42+7166A>G		intron_variant	Intron 1 of 12	1		ENSP00000364904.4
SYK	ENST00000476708.1	n.78+7020A>G		intron_variant	Intron 1 of 1	2

Frequencies

GnomAD3 genomes AF: 0.356 AC: 54103 AN: 152018 Hom.: 9773 Cov.: 32

Gnomad AFR AF: 0.352

Gnomad AMI AF: 0.507

Gnomad AMR AF: 0.456

Gnomad ASJ AF: 0.388

Gnomad EAS AF: 0.252

Gnomad SAS AF: 0.390

Gnomad FIN AF: 0.299

Gnomad MID AF: 0.487

Gnomad NFE AF: 0.345

Gnomad OTH AF: 0.376

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

GnomAD4 genome AF: 0.356 AC: 54166 AN: 152136 Hom.: 9795 Cov.: 32 AF XY: 0.357 AC XY: 26580 AN XY: 74372

African (AFR) AF: 0.353 AC: 14646 AN: 41504

American (AMR) AF: 0.456 AC: 6972 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.388 AC: 1345 AN: 3466

East Asian (EAS) AF: 0.253 AC: 1310 AN: 5168

South Asian (SAS) AF: 0.389 AC: 1875 AN: 4824

European-Finnish (FIN) AF: 0.299 AC: 3158 AN: 10576

Middle Eastern (MID) AF: 0.497 AC: 146 AN: 294

European-Non Finnish (NFE) AF: 0.345 AC: 23461 AN: 67992

Other (OTH) AF: 0.375 AC: 792 AN: 2110

Alfa AF: 0.355 Hom.: 16106

Bravo AF: 0.365

Asia WGS AF: 0.373 AC: 1296 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	11
DANN	Benign	0.66
PhyloP100		0.31
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: rs3789889; hg19: chr9-93571341;