Genetic Variant SYK:c.417+79A>G (chr9-90844394-A-G) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_003177.7(SYK):c.417+79A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.335 in 1,404,514 control chromosomes in the GnomAD database, including 78,900 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.30 ( 7098 hom., cov: 34)

Exomes 𝑓: 0.34 ( 71802 hom. )

Consequence

SYK
NM_003177.7 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -4.29

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]

SYK links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BP6

Variant 9-90844394-A-G is Benign according to our data. Variant chr9-90844394-A-G is described in ClinVar as [Benign]. Clinvar id is 2688110.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.372 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SYK	NM_003177.7 link	c.417+79A>G		intron_variant	Intron 2 of 13	ENST00000375754.9	NP_003168.2	P43405-1A0A024R244

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SYK	ENST00000375754.9 link	c.417+79A>G		intron_variant	Intron 2 of 13	1	NM_003177.7	ENSP00000364907.4		P43405-1

Frequencies

GnomAD3 genomes

AF:

0.301

AC:

45778

AN:

152068

Hom.:

7082

Cov.:

show subpopulations

Gnomad AFR

AF:

0.233

Gnomad AMI

AF:

0.218

Gnomad AMR

AF:

0.262

Gnomad ASJ

AF:

0.333

Gnomad EAS

AF:

0.369

Gnomad SAS

AF:

0.386

Gnomad FIN

AF:

0.370

Gnomad MID

AF:

0.203

Gnomad NFE

AF:

0.330

Gnomad OTH

AF:

0.281

GnomAD4 exome

AF:

0.339

AC:

424375

AN:

1252328

Hom.:

71802

AF XY:

0.340

AC XY:

207640

AN XY:

611280

show subpopulations

Gnomad4 AFR exome

AF:

0.227

Gnomad4 AMR exome

AF:

0.235

Gnomad4 ASJ exome

AF:

0.328

Gnomad4 EAS exome

AF:

0.346

Gnomad4 SAS exome

AF:

0.369

Gnomad4 FIN exome

AF:

0.374

Gnomad4 NFE exome

AF:

0.342

Gnomad4 OTH exome

AF:

0.329

GnomAD4 genome

AF:

0.301

AC:

45843

AN:

152186

Hom.:

7098

Cov.:

AF XY:

0.303

AC XY:

22548

AN XY:

74426

show subpopulations

Gnomad4 AFR

AF:

0.234

Gnomad4 AMR

AF:

0.262

Gnomad4 ASJ

AF:

0.333

Gnomad4 EAS

AF:

0.370

Gnomad4 SAS

AF:

0.386

Gnomad4 FIN

AF:

0.370

Gnomad4 NFE

AF:

0.330

Gnomad4 OTH

AF:

0.279

Alfa

AF:

0.213

Hom.:

592

Bravo

AF:

0.287

Asia WGS

AF:

0.353

AC:

1224

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Jan 24, 2024

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 53% of patients studied by a panel of primary immunodeficiencies. Number of patients: 50. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.28

DANN

Benign

0.59

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over