rs10119179

Positions:

• chr9-90870518-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003177.7(SYK):​c.915+3319G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.082 in 152,230 control chromosomes in the GnomAD database, including 648 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 0.082 (648 hom., cov: 33)
• Consequence: SYK NM_003177.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.24

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.145 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SYK	NM_003177.7	c.915+3319G>A		intron_variant		ENST00000375754.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SYK	ENST00000375754.9	c.915+3319G>A		intron_variant		1	NM_003177.7	P1
SYK	ENST00000375746.1	c.915+3319G>A		intron_variant		1		P1
SYK	ENST00000375747.5	c.847-3686G>A		intron_variant		1
SYK	ENST00000375751.8	c.847-3686G>A		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.0819 AC: 12460 AN: 152112 Hom.: 648 Cov.: 33

Gnomad AFR AF: 0.148

Gnomad AMI AF: 0.0800

Gnomad AMR AF: 0.0693

Gnomad ASJ AF: 0.0421

Gnomad EAS AF: 0.0181

Gnomad SAS AF: 0.0876

Gnomad FIN AF: 0.0683

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.0539

Gnomad OTH AF: 0.0684

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

GnomAD4 genome AF: 0.0820 AC: 12478 AN: 152230 Hom.: 648 Cov.: 33 AF XY: 0.0830 AC XY: 6176 AN XY: 74434

Gnomad4 AFR AF: 0.148

Gnomad4 AMR AF: 0.0696

Gnomad4 ASJ AF: 0.0421

Gnomad4 EAS AF: 0.0179

Gnomad4 SAS AF: 0.0870

Gnomad4 FIN AF: 0.0683

Gnomad4 NFE AF: 0.0539

Gnomad4 OTH AF: 0.0672

Alfa AF: 0.0644 Hom.: 263

Bravo AF: 0.0860

Asia WGS AF: 0.0680 AC: 238 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.078
DANN	Benign	0.24

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

Publications

LitVar

Other links and lift over

dbSNP: rs10119179; hg19: chr9-93632800;