9-90844061-G-C

Variant names:

• chr9-90844061-G-C
• rs200078199
• NM_003177.7:c.163G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_003177.7(SYK):​c.163G>C​(p.Val55Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V55M) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: SYK NM_003177.7 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.55
• Publications: 0 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), PanelApp Australia

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.20995915).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SYK	NM_003177.7	MANE Select	c.163G>C	p.Val55Leu	missense	Exon 2 of 14	NP_003168.2
	SYK	NM_001174167.3		c.163G>C	p.Val55Leu	missense	Exon 2 of 14	NP_001167638.1	P43405-1
	SYK	NM_001135052.4		c.163G>C	p.Val55Leu	missense	Exon 2 of 13	NP_001128524.1	P43405-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SYK	ENST00000375754.9	TSL:1 MANE Select	c.163G>C	p.Val55Leu	missense	Exon 2 of 14	ENSP00000364907.4	P43405-1
	SYK	ENST00000375746.1	TSL:1	c.163G>C	p.Val55Leu	missense	Exon 2 of 14	ENSP00000364898.1	P43405-1
	SYK	ENST00000375747.5	TSL:1	c.163G>C	p.Val55Leu	missense	Exon 2 of 13	ENSP00000364899.1	P43405-2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Uncertain	0.028	T
BayesDel_noAF	Benign	-0.20
CADD	Benign	21
DANN	Benign	0.94
DEOGEN2	Benign	0.37	T
Eigen	Benign	-0.13
Eigen_PC	Benign	0.055
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Uncertain	0.88	D
M_CAP	Uncertain	0.13	D
MetaRNN	Benign	0.21	T
MetaSVM	Uncertain	-0.26	T
MutationAssessor	Benign	1.4	L
PhyloP100		2.5
PrimateAI	Uncertain	0.64	T
PROVEAN	Benign	-0.040	N
REVEL	Uncertain	0.31
Sift	Benign	0.60	T
Sift4G	Benign	0.63	T
Polyphen		0.096	B
Vest4		0.057
MutPred		0.71		Loss of methylation at K60 (P = 0.0886)
MVP		0.79
MPC		0.18
ClinPred		0.49	T
GERP RS		5.0
Varity_R		0.18
gMVP		0.55
Mutation Taster		=75/25	polymorphism

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: rs200078199; hg19: chr9-93606343;