rs1333633

Variant names:

• chr9-90805290-G-A
• rs1333633
• NM_003177.7:c.-42+3397G>A

Your query was ambiguous. Multiple possible variants found:

• chr9-90805290-G-A
• chr9-90805290-G-C
• chr9-90805290-G-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+3397G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.546 in 151,980 control chromosomes in the GnomAD database, including 23,291 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 0.55 (23291 hom., cov: 32)
• Consequence: SYK NM_003177.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0300
• Publications: 10 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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.673 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SYK	NM_003177.7	c.-42+3397G>A		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+3397G>A		intron_variant	Intron 1 of 13	1	NM_003177.7	ENSP00000364907.4
SYK	ENST00000375747.5	c.-42+3285G>A		intron_variant	Intron 1 of 12	1		ENSP00000364899.1
SYK	ENST00000375751.8	c.-42+3397G>A		intron_variant	Intron 1 of 12	1		ENSP00000364904.4
SYK	ENST00000476708.1	n.78+3251G>A		intron_variant	Intron 1 of 1	2

Frequencies

GnomAD3 genomes AF: 0.546 AC: 82908 AN: 151862 Hom.: 23277 Cov.: 32

Gnomad AFR AF: 0.417

Gnomad AMI AF: 0.555

Gnomad AMR AF: 0.680

Gnomad ASJ AF: 0.560

Gnomad EAS AF: 0.692

Gnomad SAS AF: 0.585

Gnomad FIN AF: 0.691

Gnomad MID AF: 0.631

Gnomad NFE AF: 0.556

Gnomad OTH AF: 0.565

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

GnomAD4 genome AF: 0.546 AC: 82963 AN: 151980 Hom.: 23291 Cov.: 32 AF XY: 0.555 AC XY: 41263 AN XY: 74286

African (AFR) AF: 0.417 AC: 17300 AN: 41438

American (AMR) AF: 0.680 AC: 10386 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.560 AC: 1944 AN: 3472

East Asian (EAS) AF: 0.692 AC: 3571 AN: 5160

South Asian (SAS) AF: 0.585 AC: 2819 AN: 4816

European-Finnish (FIN) AF: 0.691 AC: 7311 AN: 10576

Middle Eastern (MID) AF: 0.631 AC: 183 AN: 290

European-Non Finnish (NFE) AF: 0.556 AC: 37751 AN: 67940

Other (OTH) AF: 0.566 AC: 1193 AN: 2108

Alfa AF: 0.560 Hom.: 44682

Bravo AF: 0.542

Asia WGS AF: 0.641 AC: 2231 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	6.3
DANN	Benign	0.46
PhyloP100		0.030
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: rs1333633; hg19: chr9-93567572;