rs10119179

Variant names:

• chr9-90870518-G-A
• rs10119179
• NM_003177.7:c.915+3319G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 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=-0.93).
• 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 rank	MANE	Protein	UniProt
SYK	NM_003177.7	c.915+3319G>A		intron_variant	Intron 7 of 13	ENST00000375754.9	NP_003168.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SYK	ENST00000375754.9	c.915+3319G>A		intron_variant	Intron 7 of 13	1	NM_003177.7	ENSP00000364907.4
SYK	ENST00000375746.1	c.915+3319G>A		intron_variant	Intron 7 of 13	1		ENSP00000364898.1
SYK	ENST00000375747.5	c.847-3686G>A		intron_variant	Intron 6 of 12	1		ENSP00000364899.1
SYK	ENST00000375751.8	c.847-3686G>A		intron_variant	Intron 6 of 12	1		ENSP00000364904.4

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

African (AFR) AF: 0.148 AC: 6133 AN: 41520

American (AMR) AF: 0.0696 AC: 1065 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0421 AC: 146 AN: 3472

East Asian (EAS) AF: 0.0179 AC: 93 AN: 5184

South Asian (SAS) AF: 0.0870 AC: 420 AN: 4826

European-Finnish (FIN) AF: 0.0683 AC: 724 AN: 10596

Middle Eastern (MID) AF: 0.0510 AC: 15 AN: 294

European-Non Finnish (NFE) AF: 0.0539 AC: 3667 AN: 68018

Other (OTH) AF: 0.0672 AC: 142 AN: 2114

Alfa AF: 0.0652 Hom.: 321

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
PhyloP100		-1.2
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: rs10119179; hg19: chr9-93632800;