9-90844052-G-T

Position:

• chr9-90844052-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 3P and 1B. PM2 PP2 BP6

The NM_003177.7(SYK):​c.154G>T​(p.Ala52Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency: Genomes: not found (cov: 33)
• Consequence: SYK NM_003177.7 missense
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: 7.57

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 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 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.
• BP6: Variant 9-90844052-G-T is Benign according to our data. Variant chr9-90844052-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 207858.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SYK	NM_003177.7	c.154G>T	p.Ala52Ser	missense_variant	2/14	ENST00000375754.9	NP_003168.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SYK	ENST00000375754.9	c.154G>T	p.Ala52Ser	missense_variant	2/14	1	NM_003177.7	ENSP00000364907.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

Long QT syndrome Benign:1

Likely benign, no assertion criteria provided

research

Medical Research Institute, Tokyo Medical and Dental University

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.33
BayesDel_addAF	Uncertain	0.14	D
BayesDel_noAF	Uncertain	-0.030
CADD	Uncertain	26
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.45	T;.;.;T
Eigen	Uncertain	0.41
Eigen_PC	Uncertain	0.47
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.94	.;.;D;D
M_CAP	Uncertain	0.28	D
MetaRNN	Uncertain	0.69	D;D;D;D
MetaSVM	Uncertain	0.0015	D
MutationAssessor	Benign	1.1	L;L;L;L
PrimateAI	Uncertain	0.69	T
PROVEAN	Benign	-1.8	N;N;N;N
REVEL	Uncertain	0.60
Sift	Benign	0.19	T;D;D;T
Sift4G	Uncertain	0.023	D;D;D;D
Polyphen		0.91	P;P;P;P
Vest4		0.45
MutPred		0.54		Gain of disorder (P = 0.0574);Gain of disorder (P = 0.0574);Gain of disorder (P = 0.0574);Gain of disorder (P = 0.0574);
MVP		0.83
MPC		0.63
ClinPred		0.96	D
GERP RS		5.0
Varity_R		0.47
gMVP		0.56

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: rs796052158; hg19: chr9-93606334;