NM_003177.7:c.-42+1824A>G

Variant names:

• chr9-90803717-A-G
• rs1319677
• NM_003177.7:c.-42+1824A>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+1824A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.413 in 151,936 control chromosomes in the GnomAD database, including 13,993 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 0.41 (13993 hom., cov: 31)
• Consequence: SYK NM_003177.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.72
• 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)

ENSG00000308134 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.601 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SYK	NM_003177.7	c.-42+1824A>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+1824A>G		intron_variant	Intron 1 of 13	1	NM_003177.7	ENSP00000364907.4

Frequencies

GnomAD3 genomes AF: 0.413 AC: 62710 AN: 151816 Hom.: 13996 Cov.: 31

Gnomad AFR AF: 0.241

Gnomad AMI AF: 0.431

Gnomad AMR AF: 0.442

Gnomad ASJ AF: 0.463

Gnomad EAS AF: 0.619

Gnomad SAS AF: 0.431

Gnomad FIN AF: 0.599

Gnomad MID AF: 0.459

Gnomad NFE AF: 0.462

Gnomad OTH AF: 0.422

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

GnomAD4 genome AF: 0.413 AC: 62730 AN: 151936 Hom.: 13993 Cov.: 31 AF XY: 0.420 AC XY: 31185 AN XY: 74266

African (AFR) AF: 0.241 AC: 9994 AN: 41458

American (AMR) AF: 0.441 AC: 6742 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.463 AC: 1605 AN: 3470

East Asian (EAS) AF: 0.619 AC: 3202 AN: 5174

South Asian (SAS) AF: 0.432 AC: 2083 AN: 4822

European-Finnish (FIN) AF: 0.599 AC: 6303 AN: 10524

Middle Eastern (MID) AF: 0.459 AC: 135 AN: 294

European-Non Finnish (NFE) AF: 0.462 AC: 31382 AN: 67904

Other (OTH) AF: 0.423 AC: 893 AN: 2110

Alfa AF: 0.440 Hom.: 5612

Bravo AF: 0.398

Asia WGS AF: 0.481 AC: 1673 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.22
DANN	Benign	0.52
PhyloP100		-1.7
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: rs1319677; hg19: chr9-93565999;