NM_003177.7:c.-42+20618A>G

Variant names:

• chr9-90822511-A-G
• rs914925
• NM_003177.7:c.-42+20618A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003177.7(SYK):​c.-42+20618A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.431 in 152,164 control chromosomes in the GnomAD database, including 15,879 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 0.43 (15879 hom., cov: 33)
• Consequence: SYK NM_003177.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.30
• Publications: 8 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 (SAS) allele frequency at 95% confidence interval = 0.551 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SYK	NM_003177.7	c.-42+20618A>G		intron_variant	Intron 1 of 13	ENST00000375754.9	NP_003168.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SYK	ENST00000375754.9	c.-42+20618A>G		intron_variant	Intron 1 of 13	1	NM_003177.7	ENSP00000364907.4
SYK	ENST00000375747.5	c.-42+20506A>G		intron_variant	Intron 1 of 12	1		ENSP00000364899.1
SYK	ENST00000375751.8	c.-42+20618A>G		intron_variant	Intron 1 of 12	1		ENSP00000364904.4
SYK	ENST00000476708.1	n.78+20472A>G		intron_variant	Intron 1 of 1	2

Frequencies

GnomAD3 genomes AF: 0.431 AC: 65597 AN: 152044 Hom.: 15870 Cov.: 33

Gnomad AFR AF: 0.198

Gnomad AMI AF: 0.490

Gnomad AMR AF: 0.534

Gnomad ASJ AF: 0.516

Gnomad EAS AF: 0.397

Gnomad SAS AF: 0.568

Gnomad FIN AF: 0.438

Gnomad MID AF: 0.427

Gnomad NFE AF: 0.536

Gnomad OTH AF: 0.473

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.431 AC: 65644 AN: 152164 Hom.: 15879 Cov.: 33 AF XY: 0.432 AC XY: 32117 AN XY: 74388

African (AFR) AF: 0.198 AC: 8236 AN: 41512

American (AMR) AF: 0.534 AC: 8170 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.516 AC: 1791 AN: 3472

East Asian (EAS) AF: 0.397 AC: 2054 AN: 5174

South Asian (SAS) AF: 0.568 AC: 2739 AN: 4818

European-Finnish (FIN) AF: 0.438 AC: 4630 AN: 10580

Middle Eastern (MID) AF: 0.428 AC: 125 AN: 292

European-Non Finnish (NFE) AF: 0.536 AC: 36456 AN: 68008

Other (OTH) AF: 0.473 AC: 996 AN: 2104

Alfa AF: 0.509 Hom.: 33946

Bravo AF: 0.423

Asia WGS AF: 0.493 AC: 1714 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	0.12
DANN	Benign	0.59
PhyloP100		-1.3
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: rs914925; hg19: chr9-93584793;