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

Variant summary

Our verdict is Benign. The variant received -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

Publications

6 publications found

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 Gene-Disease associations (from GenCC):

immunodeficiency 82 with systemic inflammation
Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), PanelApp Australia

SYK links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003177.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SYK	NM_003177.7	MANE Select	c.417+79A>G	intron	N/A	NP_003168.2
SYK	NM_001174167.3		c.417+79A>G	intron	N/A	NP_001167638.1	P43405-1
SYK	NM_001135052.4		c.417+79A>G	intron	N/A	NP_001128524.1	P43405-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SYK	ENST00000375754.9	TSL:1 MANE Select	c.417+79A>G	intron	N/A	ENSP00000364907.4	P43405-1
SYK	ENST00000375746.1	TSL:1	c.417+79A>G	intron	N/A	ENSP00000364898.1	P43405-1
SYK	ENST00000375747.5	TSL:1	c.417+79A>G	intron	N/A	ENSP00000364899.1	P43405-2

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

African (AFR)

AF:

0.227

AC:

6245

AN:

27456

American (AMR)

AF:

0.235

AC:

4691

AN:

19928

Ashkenazi Jewish (ASJ)

AF:

0.328

AC:

6106

AN:

18622

East Asian (EAS)

AF:

0.346

AC:

12023

AN:

34736

South Asian (SAS)

AF:

0.369

AC:

22948

AN:

62242

European-Finnish (FIN)

AF:

0.374

AC:

13124

AN:

35100

Middle Eastern (MID)

AF:

0.205

AC:

1056

AN:

5144

European-Non Finnish (NFE)

AF:

0.342

AC:

340920

AN:

996576

Other (OTH)

AF:

0.329

AC:

17262

AN:

52524

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

14052

28104

42155

56207

70259

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

11368

22736

34104

45472

56840

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.301

AC:

45843

AN:

152186

Hom.:

7098

Cov.:

AF XY:

0.303

AC XY:

22548

AN XY:

74426

show subpopulations

African (AFR)

AF:

0.234

AC:

9714

AN:

41534

American (AMR)

AF:

0.262

AC:

4009

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.333

AC:

1155

AN:

3470

East Asian (EAS)

AF:

0.370

AC:

1914

AN:

5172

South Asian (SAS)

AF:

0.386

AC:

1861

AN:

4816

European-Finnish (FIN)

AF:

0.370

AC:

3926

AN:

10602

Middle Eastern (MID)

AF:

0.204

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.330

AC:

22414

AN:

67982

Other (OTH)

AF:

0.279

AC:

591

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1716

3432

5147

6863

8579

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

480

960

1440

1920

2400

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.213

Hom.:

611

Bravo

AF:

0.287

Asia WGS

AF:

0.353

AC:

1224

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.28

(source)

DANN

Benign

0.59

PhyloP100

-4.3

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over