NM_003177.7:c.578+1543A>G

Variant names:

• chr9-90847137-A-G
• rs2035073
• NM_003177.7:c.578+1543A>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.578+1543A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.299 in 152,194 control chromosomes in the GnomAD database, including 7,016 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 0.30 (7016 hom., cov: 33)
• Consequence: SYK NM_003177.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.56
• 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)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.372 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SYK	NM_003177.7	c.578+1543A>G		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.578+1543A>G		intron_variant	Intron 3 of 13	1	NM_003177.7	ENSP00000364907.4
SYK	ENST00000375746.1	c.578+1543A>G		intron_variant	Intron 3 of 13	1		ENSP00000364898.1
SYK	ENST00000375747.5	c.578+1543A>G		intron_variant	Intron 3 of 12	1		ENSP00000364899.1
SYK	ENST00000375751.8	c.578+1543A>G		intron_variant	Intron 3 of 12	1		ENSP00000364904.4

Frequencies

GnomAD3 genomes AF: 0.299 AC: 45439 AN: 152078 Hom.: 7000 Cov.: 33

Gnomad AFR AF: 0.226

Gnomad AMI AF: 0.218

Gnomad AMR AF: 0.261

Gnomad ASJ AF: 0.333

Gnomad EAS AF: 0.368

Gnomad SAS AF: 0.386

Gnomad FIN AF: 0.371

Gnomad MID AF: 0.203

Gnomad NFE AF: 0.329

Gnomad OTH AF: 0.279

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

GnomAD4 genome AF: 0.299 AC: 45502 AN: 152194 Hom.: 7016 Cov.: 33 AF XY: 0.301 AC XY: 22390 AN XY: 74398

African (AFR) AF: 0.226 AC: 9398 AN: 41532

American (AMR) AF: 0.262 AC: 3999 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.333 AC: 1155 AN: 3470

East Asian (EAS) AF: 0.369 AC: 1904 AN: 5164

South Asian (SAS) AF: 0.386 AC: 1865 AN: 4828

European-Finnish (FIN) AF: 0.371 AC: 3929 AN: 10586

Middle Eastern (MID) AF: 0.204 AC: 60 AN: 294

European-Non Finnish (NFE) AF: 0.329 AC: 22407 AN: 68006

Other (OTH) AF: 0.278 AC: 586 AN: 2110

Alfa AF: 0.322 Hom.: 34121

Bravo AF: 0.284

Asia WGS AF: 0.353 AC: 1224 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.16
DANN	Benign	0.71
PhyloP100		-1.6
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: rs2035073; hg19: chr9-93609419; COSMIC: COSV65326156; COSMIC: COSV65326156;