Genetic Variant NM_003177.7:c.-41-37G>A (chr9-90843821-G-A) – 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.-41-37G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.266 in 1,382,802 control chromosomes in the GnomAD database, including 52,035 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.31 ( 7874 hom., cov: 32)

Exomes 𝑓: 0.26 ( 44161 hom. )

Consequence

SYK
NM_003177.7 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.834

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=-0.84).

BP6

Variant 9-90843821-G-A is Benign according to our data. Variant chr9-90843821-G-A is described in ClinVar as [Benign]. Clinvar id is 2688069.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.413 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SYK	NM_003177.7 link	c.-41-37G>A		intron_variant	Intron 1 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.-41-37G>A		intron_variant	Intron 1 of 13	1	NM_003177.7	ENSP00000364907.4		P43405-1

Frequencies

GnomAD3 genomes

AF:

0.306

AC:

46427

AN:

151888

Hom.:

7865

Cov.:

show subpopulations

Gnomad AFR

AF:

0.419

Gnomad AMI

AF:

0.455

Gnomad AMR

AF:

0.365

Gnomad ASJ

AF:

0.295

Gnomad EAS

AF:

0.0323

Gnomad SAS

AF:

0.225

Gnomad FIN

AF:

0.155

Gnomad MID

AF:

0.370

Gnomad NFE

AF:

0.272

Gnomad OTH

AF:

0.309

GnomAD4 exome

AF:

0.261

AC:

321420

AN:

1230794

Hom.:

44161

Cov.:

AF XY:

0.261

AC XY:

155011

AN XY:

594188

show subpopulations

Gnomad4 AFR exome

AF:

0.432

Gnomad4 AMR exome

AF:

0.376

Gnomad4 ASJ exome

AF:

0.296

Gnomad4 EAS exome

AF:

0.0234

Gnomad4 SAS exome

AF:

0.223

Gnomad4 FIN exome

AF:

0.170

Gnomad4 NFE exome

AF:

0.266

Gnomad4 OTH exome

AF:

0.263

GnomAD4 genome

AF:

0.306

AC:

46464

AN:

152008

Hom.:

7874

Cov.:

AF XY:

0.299

AC XY:

22225

AN XY:

74314

show subpopulations

Gnomad4 AFR

AF:

0.418

Gnomad4 AMR

AF:

0.365

Gnomad4 ASJ

AF:

0.295

Gnomad4 EAS

AF:

0.0322

Gnomad4 SAS

AF:

0.225

Gnomad4 FIN

AF:

0.155

Gnomad4 NFE

AF:

0.272

Gnomad4 OTH

AF:

0.308

Alfa

AF:

0.274

Hom.:

7935

Bravo

AF:

0.327

Asia WGS

AF:

0.167

AC:

581

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 61% of patients studied by a panel of primary immunodeficiencies. Number of patients: 58. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

1.0

DANN

Benign

0.62

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