rs1049164

Positions:

• chr9-90895924-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003177.7(SYK):​c.*324G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.184 in 357,832 control chromosomes in the GnomAD database, including 6,618 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 0.18 (2671 hom., cov: 32)
  • Exomes 𝑓: 0.19 (3947 hom.)
• Consequence: SYK NM_003177.7 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.924

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.247 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SYK	NM_003177.7	c.*324G>A		3_prime_UTR_variant	14/14	ENST00000375754.9	NP_003168.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SYK	ENST00000375754.9	c.*324G>A		3_prime_UTR_variant	14/14	1	NM_003177.7	ENSP00000364907	P1
SYK	ENST00000375746.1	c.*324G>A		3_prime_UTR_variant	14/14	1		ENSP00000364898	P1
SYK	ENST00000375747.5	c.*324G>A		3_prime_UTR_variant	13/13	1		ENSP00000364899
SYK	ENST00000375751.8	c.*324G>A		3_prime_UTR_variant	13/13	1		ENSP00000364904

Frequencies

GnomAD3 genomes AF: 0.178 AC: 27041 AN: 151912 Hom.: 2671 Cov.: 32

Gnomad AFR AF: 0.131

Gnomad AMI AF: 0.0879

Gnomad AMR AF: 0.160

Gnomad ASJ AF: 0.220

Gnomad EAS AF: 0.105

Gnomad SAS AF: 0.259

Gnomad FIN AF: 0.266

Gnomad MID AF: 0.217

Gnomad NFE AF: 0.196

Gnomad OTH AF: 0.164

GnomAD4 exome AF: 0.188 AC: 38613 AN: 205802 Hom.: 3947 Cov.: 0 AF XY: 0.192 AC XY: 19893 AN XY: 103392

Gnomad4 AFR exome AF: 0.130

Gnomad4 AMR exome AF: 0.170

Gnomad4 ASJ exome AF: 0.216

Gnomad4 EAS exome AF: 0.0988

Gnomad4 SAS exome AF: 0.244

Gnomad4 FIN exome AF: 0.252

Gnomad4 NFE exome AF: 0.191

Gnomad4 OTH exome AF: 0.185

GnomAD4 genome AF: 0.178 AC: 27053 AN: 152030 Hom.: 2671 Cov.: 32 AF XY: 0.179 AC XY: 13333 AN XY: 74288

Gnomad4 AFR AF: 0.131

Gnomad4 AMR AF: 0.159

Gnomad4 ASJ AF: 0.220

Gnomad4 EAS AF: 0.105

Gnomad4 SAS AF: 0.259

Gnomad4 FIN AF: 0.266

Gnomad4 NFE AF: 0.196

Gnomad4 OTH AF: 0.162

Alfa AF: 0.191 Hom.: 3806

Bravo AF: 0.163

Asia WGS AF: 0.160 AC: 556 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	8.0
DANN	Benign	0.63

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

Publications

LitVar

Other links and lift over

dbSNP: rs1049164; hg19: chr9-93658206;