9-90844052-G-T

Variant names:

• chr9-90844052-G-T
• rs796052158
• NM_003177.7:c.154G>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 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
• Publications: 5 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: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• 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 VariationId is 207858.Status of the report is no_assertion_criteria_provided, 0 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003177.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SYK	NM_003177.7	MANE Select	c.154G>T	p.Ala52Ser	missense	Exon 2 of 14	NP_003168.2
	SYK	NM_001174167.3		c.154G>T	p.Ala52Ser	missense	Exon 2 of 14	NP_001167638.1
	SYK	NM_001135052.4		c.154G>T	p.Ala52Ser	missense	Exon 2 of 13	NP_001128524.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SYK	ENST00000375754.9	TSL:1 MANE Select	c.154G>T	p.Ala52Ser	missense	Exon 2 of 14	ENSP00000364907.4
	SYK	ENST00000375746.1	TSL:1	c.154G>T	p.Ala52Ser	missense	Exon 2 of 14	ENSP00000364898.1
	SYK	ENST00000375747.5	TSL:1	c.154G>T	p.Ala52Ser	missense	Exon 2 of 13	ENSP00000364899.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	Long QT syndrome (1)

Computational scores

Source: dbNSFP v4.9

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
Eigen	Uncertain	0.41
Eigen_PC	Uncertain	0.47
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.94	D
M_CAP	Uncertain	0.28	D
MetaRNN	Uncertain	0.69	D
MetaSVM	Uncertain	0.0015	D
MutationAssessor	Benign	1.1	L
PhyloP100		7.6
PrimateAI	Uncertain	0.69	T
PROVEAN	Benign	-1.8	N
REVEL	Uncertain	0.60
Sift	Benign	0.19	T
Sift4G	Uncertain	0.023	D
Polyphen		0.91	P
Vest4		0.45
MutPred		0.54		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
Mutation Taster		=28/72	disease causing

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: rs796052158; hg19: chr9-93606334;