rs10993738

Variant names:

• chr9-90870958-A-C
• rs10993738
• NM_003177.7:c.916-3246A>C

Your query was ambiguous. Multiple possible variants found:

• chr9-90870958-A-C
• chr9-90870958-A-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.916-3246A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0162 in 152,364 control chromosomes in the GnomAD database, including 178 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 0.016 (178 hom., cov: 33)
• Consequence: SYK NM_003177.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.411
• Publications: 16 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=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.208 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SYK	NM_003177.7	c.916-3246A>C		intron_variant	Intron 7 of 13	ENST00000375754.9	NP_003168.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SYK	ENST00000375754.9	c.916-3246A>C		intron_variant	Intron 7 of 13	1	NM_003177.7	ENSP00000364907.4
SYK	ENST00000375746.1	c.916-3246A>C		intron_variant	Intron 7 of 13	1		ENSP00000364898.1
SYK	ENST00000375747.5	c.847-3246A>C		intron_variant	Intron 6 of 12	1		ENSP00000364899.1
SYK	ENST00000375751.8	c.847-3246A>C		intron_variant	Intron 6 of 12	1		ENSP00000364904.4

Frequencies

GnomAD3 genomes AF: 0.0162 AC: 2468 AN: 152246 Hom.: 177 Cov.: 33

Gnomad AFR AF: 0.00210

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0101

Gnomad ASJ AF: 0.0150

Gnomad EAS AF: 0.219

Gnomad SAS AF: 0.0987

Gnomad FIN AF: 0.00527

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00680

Gnomad OTH AF: 0.0186

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

GnomAD4 genome AF: 0.0162 AC: 2465 AN: 152364 Hom.: 178 Cov.: 33 AF XY: 0.0181 AC XY: 1347 AN XY: 74506

African (AFR) AF: 0.00209 AC: 87 AN: 41592

American (AMR) AF: 0.0101 AC: 154 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0150 AC: 52 AN: 3470

East Asian (EAS) AF: 0.219 AC: 1137 AN: 5190

South Asian (SAS) AF: 0.0984 AC: 475 AN: 4828

European-Finnish (FIN) AF: 0.00527 AC: 56 AN: 10622

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.00681 AC: 463 AN: 68036

Other (OTH) AF: 0.0180 AC: 38 AN: 2116

Alfa AF: 0.0147 Hom.: 155

Bravo AF: 0.0152

Asia WGS AF: 0.127 AC: 442 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.42
DANN	Benign	0.60
PhyloP100		-0.41
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: rs10993738; hg19: chr9-93633240; COSMIC: COSV65326228;