rs780001574

Variant names:

• chr15-74799325-C-G
• rs780001574
• NM_004383.3:c.296C>G

Your query was ambiguous. Multiple possible variants found:

• chr15-74799325-C-G
• chr15-74799325-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_004383.3(CSK):​c.296C>G​(p.Pro99Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000657 in 152,182 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
• Consequence: CSK NM_004383.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.81

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CSK	NM_004383.3	c.296C>G	p.Pro99Arg	missense_variant	Exon 5 of 13	ENST00000220003.14	NP_004374.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CSK	ENST00000220003.14	c.296C>G	p.Pro99Arg	missense_variant	Exon 5 of 13	1	NM_004383.3	ENSP00000220003.9

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152182 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

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: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152182 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 74344

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000147

Gnomad4 OTH AF: 0.00

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.32
BayesDel_addAF	Pathogenic	0.36	D
BayesDel_noAF	Pathogenic	0.27
CADD	Benign	23
DANN	Benign	0.95
DEOGEN2	Uncertain	0.54	D;D;T;.;D
Eigen	Benign	-0.28
Eigen_PC	Benign	-0.087
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.91	.;.;D;D;D
M_CAP	Benign	0.075	D
MetaRNN	Uncertain	0.73	D;D;D;D;D
MetaSVM	Benign	-0.47	T
MutationAssessor	Benign	0.40	N;N;.;.;N
PrimateAI	Uncertain	0.74	T
PROVEAN	Benign	0.79	N;N;N;N;N
REVEL	Uncertain	0.58
Sift	Benign	0.74	T;T;T;T;T
Sift4G	Benign	0.81	T;T;T;T;T
Polyphen		0.0040	B;B;.;.;B
Vest4		0.66
MutPred		0.65		Loss of glycosylation at P99 (P = 0.0341);Loss of glycosylation at P99 (P = 0.0341);.;Loss of glycosylation at P99 (P = 0.0341);Loss of glycosylation at P99 (P = 0.0341);
MVP		0.96
MPC		2.1
ClinPred		0.82	D
GERP RS		4.6
Varity_R		0.50
gMVP		0.85

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

Other links and lift over

dbSNP: rs780001574; hg19: chr15-75091666;