rs10761395

Variant names:

• chr9-90880615-T-C
• rs10761395
• NM_003177.7:c.1581+1662T>C

Variant summary

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

The NM_003177.7(SYK):​c.1581+1662T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.307 in 152,008 control chromosomes in the GnomAD database, including 7,758 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 0.31 (7758 hom., cov: 32)
• Consequence: SYK NM_003177.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.463
• Publications: 10 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 (AFR) allele frequency at 95% confidence interval = 0.364 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SYK	NM_003177.7	c.1581+1662T>C		intron_variant	Intron 11 of 13	ENST00000375754.9	NP_003168.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SYK	ENST00000375754.9	c.1581+1662T>C		intron_variant	Intron 11 of 13	1	NM_003177.7	ENSP00000364907.4
SYK	ENST00000375746.1	c.1581+1662T>C		intron_variant	Intron 11 of 13	1		ENSP00000364898.1
SYK	ENST00000375747.5	c.1512+1662T>C		intron_variant	Intron 10 of 12	1		ENSP00000364899.1
SYK	ENST00000375751.8	c.1512+1662T>C		intron_variant	Intron 10 of 12	1		ENSP00000364904.4

Frequencies

GnomAD3 genomes AF: 0.307 AC: 46630 AN: 151890 Hom.: 7757 Cov.: 32

Gnomad AFR AF: 0.369

Gnomad AMI AF: 0.207

Gnomad AMR AF: 0.258

Gnomad ASJ AF: 0.340

Gnomad EAS AF: 0.00444

Gnomad SAS AF: 0.135

Gnomad FIN AF: 0.219

Gnomad MID AF: 0.386

Gnomad NFE AF: 0.328

Gnomad OTH AF: 0.340

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

GnomAD4 genome AF: 0.307 AC: 46639 AN: 152008 Hom.: 7758 Cov.: 32 AF XY: 0.297 AC XY: 22089 AN XY: 74322

African (AFR) AF: 0.369 AC: 15276 AN: 41436

American (AMR) AF: 0.257 AC: 3931 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.340 AC: 1181 AN: 3472

East Asian (EAS) AF: 0.00445 AC: 23 AN: 5164

South Asian (SAS) AF: 0.134 AC: 644 AN: 4820

European-Finnish (FIN) AF: 0.219 AC: 2311 AN: 10562

Middle Eastern (MID) AF: 0.384 AC: 113 AN: 294

European-Non Finnish (NFE) AF: 0.328 AC: 22256 AN: 67952

Other (OTH) AF: 0.338 AC: 715 AN: 2114

Alfa AF: 0.322 Hom.: 25390

Bravo AF: 0.313

Asia WGS AF: 0.0830 AC: 288 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.058
DANN	Benign	0.50
PhyloP100		-0.46
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs10761395; hg19: chr9-93642897;