rs750380440

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_ModerateBP6_Moderate

The NM_004383.3(CSK):c.290A>G(p.Tyr97Cys) variant causes a missense change. The variant allele was found at a frequency of 0.00000124 in 1,611,472 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Y97H) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

CSK
NM_004383.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 4.97

Publications

1 publications found

Variant links:

Genes affected

CSK (HGNC:2444): (C-terminal Src kinase) The protein encoded by this gene is involved in multiple pathways, including the regulation of Src family kinases. It plays an important role in T-cell activation through its association with the protein encoded by the protein tyrosine phosphatase, non-receptor type 22 (PTPN22) gene. This protein also phosphorylates C-terminal tyrosine residues on multiple substrates, including the protein encoded by the SRC proto-oncogene, non-receptor tyrosine kinase gene. Phosphorylation suppresses the kinase activity of the Src family tyrosine kinases. An intronic polymorphism (rs34933034) in this gene has been found to affect B-cell activation and is associated with systemic lupus erythematosus (SLE). Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2017]

CSK links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.16076925).

BP6

Variant 15-74799319-A-G is Benign according to our data. Variant chr15-74799319-A-G is described in ClinVar as Likely_benign. ClinVar VariationId is 3497598.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004383.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CSK	NM_004383.3	MANE Select	c.290A>G	p.Tyr97Cys	missense	Exon 5 of 13	NP_004374.1	B2R6Q4
CSK	NM_001127190.2		c.290A>G	p.Tyr97Cys	missense	Exon 6 of 14	NP_001120662.1	P41240
CSK	NM_001354988.2		c.290A>G	p.Tyr97Cys	missense	Exon 7 of 15	NP_001341917.1	P41240

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CSK	ENST00000220003.14	TSL:1 MANE Select	c.290A>G	p.Tyr97Cys	missense	Exon 5 of 13	ENSP00000220003.9	P41240
CSK	ENST00000439220.6	TSL:2	c.290A>G	p.Tyr97Cys	missense	Exon 6 of 14	ENSP00000414764.2	P41240
CSK	ENST00000567571.5	TSL:2	c.290A>G	p.Tyr97Cys	missense	Exon 7 of 15	ENSP00000454906.1	P41240

Frequencies

GnomAD3 genomes

AF:

0.00000658

AC:

AN:

151970

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000402

AC:

AN:

249056

AF XY:

0.00000741

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000290

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1459502

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726104

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33442

American (AMR)

AF:

0.0000224

AC:

AN:

44714

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26126

East Asian (EAS)

AF:

0.00

AC:

AN:

39694

South Asian (SAS)

AF:

0.00

AC:

AN:

86200

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52446

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4742

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111888

Other (OTH)

AF:

0.00

AC:

AN:

60250

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.00000658

AC:

AN:

151970

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74244

show subpopulations

African (AFR)

AF:

0.0000242

AC:

AN:

41356

American (AMR)

AF:

0.00

AC:

AN:

15264

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3464

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.00

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10602

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67964

Other (OTH)

AF:

0.00

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

ClinVar

ClinVar submissions

Significance:Likely 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

AlphaMissense

Benign

0.072

BayesDel_addAF

Uncertain

0.060

BayesDel_noAF

Benign

-0.15

CADD

Benign

(source)

DANN

Benign

0.97

DEOGEN2

Uncertain

0.59

Eigen

Benign

-0.19

Eigen_PC

Benign

-0.049

FATHMM_MKL

Uncertain

0.79

LIST_S2

Uncertain

0.87

M_CAP

Benign

0.051

MetaRNN

Benign

0.16

MetaSVM

Benign

-0.35

MutationAssessor

Benign

0.58

PhyloP100

5.0

PrimateAI

Benign

0.38

PROVEAN

Benign

-0.83

REVEL

Uncertain

0.32

Sift

Benign

0.21

Sift4G

Benign

0.18

Polyphen

0.0

Vest4

0.18

MutPred

0.37

Loss of disorder (P = 0.1391)

MVP

0.72

MPC

1.5

ClinPred

0.17

GERP RS

3.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.59

gMVP

0.93

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over