NM_003177.7:c.846+648A>G

Variant names:

• chr9-90865745-A-G
• rs2991216
• NM_003177.7:c.846+648A>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.846+648A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.21 in 151,916 control chromosomes in the GnomAD database, including 3,663 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 0.21 (3663 hom., cov: 31)
• Consequence: SYK NM_003177.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.220
• Publications: 7 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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.254 is higher than 0.05.

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.846+648A>G		intron	N/A	NP_003168.2
	SYK	NM_001174167.3		c.846+648A>G		intron	N/A	NP_001167638.1
	SYK	NM_001135052.4		c.846+648A>G		intron	N/A	NP_001128524.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SYK	ENST00000375754.9	TSL:1 MANE Select	c.846+648A>G		intron	N/A	ENSP00000364907.4
	SYK	ENST00000375746.1	TSL:1	c.846+648A>G		intron	N/A	ENSP00000364898.1
	SYK	ENST00000375747.5	TSL:1	c.846+648A>G		intron	N/A	ENSP00000364899.1

Frequencies

GnomAD3 genomes AF: 0.210 AC: 31903 AN: 151798 Hom.: 3661 Cov.: 31

Gnomad AFR AF: 0.128

Gnomad AMI AF: 0.0779

Gnomad AMR AF: 0.166

Gnomad ASJ AF: 0.198

Gnomad EAS AF: 0.266

Gnomad SAS AF: 0.248

Gnomad FIN AF: 0.274

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.257

Gnomad OTH AF: 0.194

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

GnomAD4 genome AF: 0.210 AC: 31920 AN: 151916 Hom.: 3663 Cov.: 31 AF XY: 0.209 AC XY: 15541 AN XY: 74250

African (AFR) AF: 0.128 AC: 5290 AN: 41436

American (AMR) AF: 0.166 AC: 2540 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.198 AC: 687 AN: 3472

East Asian (EAS) AF: 0.266 AC: 1371 AN: 5150

South Asian (SAS) AF: 0.248 AC: 1194 AN: 4814

European-Finnish (FIN) AF: 0.274 AC: 2888 AN: 10528

Middle Eastern (MID) AF: 0.112 AC: 33 AN: 294

European-Non Finnish (NFE) AF: 0.257 AC: 17442 AN: 67928

Other (OTH) AF: 0.192 AC: 404 AN: 2106

Alfa AF: 0.242 Hom.: 13947

Bravo AF: 0.196

Asia WGS AF: 0.221 AC: 770 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.7
DANN	Benign	0.47
PhyloP100		0.22
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: rs2991216; hg19: chr9-93628027; COSMIC: COSV65326217;