9-90867180-C-G

Position:

• chr9-90867180-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP2

The NM_003177.7(SYK):​c.896C>G​(p.Pro299Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SYK NM_003177.7 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.54

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 Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP2: Missense variant in gene, where missense usually causes diseases (based on misZ statistic), SYK. . Gene score misZ 2.9041 (greater than the threshold 3.09). Trascript score misZ 3.945 (greater than threshold 3.09). GenCC has associacion of gene with immunodeficiency 82 with systemic inflammation.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SYK	NM_003177.7	c.896C>G	p.Pro299Arg	missense_variant	7/14	ENST00000375754.9	NP_003168.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SYK	ENST00000375754.9	c.896C>G	p.Pro299Arg	missense_variant	7/14	1	NM_003177.7	ENSP00000364907.4
SYK	ENST00000375746.1	c.896C>G	p.Pro299Arg	missense_variant	7/14	1		ENSP00000364898.1
SYK	ENST00000375747.5	c.846+2083C>G		intron_variant		1		ENSP00000364899.1
SYK	ENST00000375751.8	c.846+2083C>G		intron_variant		1		ENSP00000364904.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Oct 01, 2024

SYK: PM2, BP4 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.41
BayesDel_addAF	Pathogenic	0.32	D
BayesDel_noAF	Pathogenic	0.22
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.33	T;T
Eigen	Uncertain	0.25
Eigen_PC	Uncertain	0.34
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.83	.;T
M_CAP	Benign	0.037	D
MetaRNN	Uncertain	0.53	D;D
MetaSVM	Benign	-0.44	T
MutationAssessor	Benign	1.6	L;L
PrimateAI	Uncertain	0.58	T
PROVEAN	Benign	-1.8	N;N
REVEL	Uncertain	0.32
Sift	Uncertain	0.013	D;D
Sift4G	Benign	0.78	T;T
Polyphen		0.31	B;B
Vest4		0.61
MutPred		0.28		Gain of MoRF binding (P = 0.0112);Gain of MoRF binding (P = 0.0112);
MVP		0.96
MPC		0.84
ClinPred		0.75	D
GERP RS		4.2
Varity_R		0.13
gMVP		0.73

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.13		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr9-93629462;