Menu
GeneBe

9-90874733-C-T

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1

The NM_003177.7(SYK):c.1065C>T(p.Pro355=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.157 in 1,613,792 control chromosomes in the GnomAD database, including 22,523 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.18 ( 2934 hom., cov: 32)
Exomes 𝑓: 0.15 ( 19589 hom. )

Consequence

SYK
NM_003177.7 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -5.12
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.68).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 9-90874733-C-T is Benign according to our data. Variant chr9-90874733-C-T is described in ClinVar as [Benign]. Clinvar id is 2688051.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-5.12 with no splicing effect.
BA1
?
    BA1 - Allele frequency is >5% in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.294 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SYKNM_003177.7 linkuse as main transcriptc.1065C>T p.Pro355= synonymous_variant 9/14 ENST00000375754.9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SYKENST00000375754.9 linkuse as main transcriptc.1065C>T p.Pro355= synonymous_variant 9/141 NM_003177.7 P1P43405-1
SYKENST00000375746.1 linkuse as main transcriptc.1065C>T p.Pro355= synonymous_variant 9/141 P1P43405-1
SYKENST00000375747.5 linkuse as main transcriptc.996C>T p.Pro332= synonymous_variant 8/131 P43405-2
SYKENST00000375751.8 linkuse as main transcriptc.996C>T p.Pro332= synonymous_variant 8/131 P43405-2

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.184
AC:
27989
AN:
151830
Hom.:
2922
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.208
Gnomad AMI
AF:
0.345
Gnomad AMR
AF:
0.301
Gnomad ASJ
AF:
0.202
Gnomad EAS
AF:
0.233
Gnomad SAS
AF:
0.100
Gnomad FIN
AF:
0.191
Gnomad MID
AF:
0.196
Gnomad NFE
AF:
0.142
Gnomad OTH
AF:
0.182
GnomAD3 exomes
AF:
0.194
AC:
48818
AN:
251438
Hom.:
6144
AF XY:
0.181
AC XY:
24542
AN XY:
135894
show subpopulations
Gnomad AFR exome
AF:
0.206
Gnomad AMR exome
AF:
0.416
Gnomad ASJ exome
AF:
0.202
Gnomad EAS exome
AF:
0.234
Gnomad SAS exome
AF:
0.104
Gnomad FIN exome
AF:
0.198
Gnomad NFE exome
AF:
0.143
Gnomad OTH exome
AF:
0.174
GnomAD4 exome
AF:
0.154
AC:
225468
AN:
1461842
Hom.:
19589
Cov.:
33
AF XY:
0.151
AC XY:
110139
AN XY:
727228
show subpopulations
Gnomad4 AFR exome
AF:
0.208
Gnomad4 AMR exome
AF:
0.405
Gnomad4 ASJ exome
AF:
0.204
Gnomad4 EAS exome
AF:
0.201
Gnomad4 SAS exome
AF:
0.109
Gnomad4 FIN exome
AF:
0.198
Gnomad4 NFE exome
AF:
0.141
Gnomad4 OTH exome
AF:
0.160
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.184
AC:
28027
AN:
151950
Hom.:
2934
Cov.:
32
AF XY:
0.186
AC XY:
13845
AN XY:
74262
show subpopulations
Gnomad4 AFR
AF:
0.208
Gnomad4 AMR
AF:
0.302
Gnomad4 ASJ
AF:
0.202
Gnomad4 EAS
AF:
0.234
Gnomad4 SAS
AF:
0.101
Gnomad4 FIN
AF:
0.191
Gnomad4 NFE
AF:
0.142
Gnomad4 OTH
AF:
0.182
Alfa
AF:
0.152
Hom.:
4524
Bravo
AF:
0.196
Asia WGS
AF:
0.170
AC:
589
AN:
3478
EpiCase
AF:
0.139
EpiControl
AF:
0.137

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Benign:1
Benign, criteria provided, single submitterclinical testingUnidad de Genómica Garrahan, Hospital de Pediatría GarrahanJan 24, 2024This variant is classified as Benign based on local population frequency. This variant was detected in 63% of patients studied by a panel of primary immunodeficiencies. Number of patients: 60. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.68
Cadd
Benign
0.19
Dann
Benign
0.77

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs2290890; hg19: chr9-93637015; COSMIC: COSV65324914; API