rs1049164

Variant names:

• chr9-90895924-G-A
• rs1049164
• NM_003177.7:c.*324G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 15 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=-0.77).
• 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 rank	MANE	Protein	UniProt
SYK	NM_003177.7	c.*324G>A		3_prime_UTR_variant	Exon 14 of 14	ENST00000375754.9	NP_003168.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SYK	ENST00000375754.9	c.*324G>A		3_prime_UTR_variant	Exon 14 of 14	1	NM_003177.7	ENSP00000364907.4
SYK	ENST00000375746.1	c.*324G>A		3_prime_UTR_variant	Exon 14 of 14	1		ENSP00000364898.1
SYK	ENST00000375747.5	c.*324G>A		3_prime_UTR_variant	Exon 13 of 13	1		ENSP00000364899.1
SYK	ENST00000375751.8	c.*324G>A		3_prime_UTR_variant	Exon 13 of 13	1		ENSP00000364904.4

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

African (AFR) AF: 0.130 AC: 1103 AN: 8466

American (AMR) AF: 0.170 AC: 1611 AN: 9452

Ashkenazi Jewish (ASJ) AF: 0.216 AC: 1774 AN: 8204

East Asian (EAS) AF: 0.0988 AC: 1771 AN: 17920

South Asian (SAS) AF: 0.244 AC: 5019 AN: 20588

European-Finnish (FIN) AF: 0.252 AC: 1684 AN: 6680

Middle Eastern (MID) AF: 0.191 AC: 181 AN: 948

European-Non Finnish (NFE) AF: 0.191 AC: 23022 AN: 120306

Other (OTH) AF: 0.185 AC: 2448 AN: 13238

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

African (AFR) AF: 0.131 AC: 5446 AN: 41450

American (AMR) AF: 0.159 AC: 2438 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.220 AC: 764 AN: 3468

East Asian (EAS) AF: 0.105 AC: 540 AN: 5166

South Asian (SAS) AF: 0.259 AC: 1250 AN: 4818

European-Finnish (FIN) AF: 0.266 AC: 2806 AN: 10550

Middle Eastern (MID) AF: 0.223 AC: 65 AN: 292

European-Non Finnish (NFE) AF: 0.196 AC: 13323 AN: 67978

Other (OTH) AF: 0.162 AC: 341 AN: 2106

Alfa AF: 0.188 Hom.: 4618

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
PhyloP100		0.92
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: rs1049164; hg19: chr9-93658206;