rs9303542

chr17-48334138-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003726.4(SKAP1):c.280+11767T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.334 in 151,674 control chromosomes in the GnomAD database, including 9,134 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.33 (9134 hom., cov: 32)
• Consequence: SKAP1 NM_003726.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.82

Genes affected

SKAP1 (HGNC:15605): (src kinase associated phosphoprotein 1) This gene encodes a T cell adaptor protein, a class of intracellular molecules with modular domains capable of recruiting additional proteins but that exhibit no intrinsic enzymatic activity. The encoded protein contains a unique N-terminal region followed by a PH domain and C-terminal SH3 domain. Along with the adhesion and degranulation-promoting adaptor protein, the encoded protein plays a critical role in inside-out signaling by coupling T-cell antigen receptor stimulation to the activation of integrins. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.463 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SKAP1	NM_003726.4	c.280+11767T>C		intron_variant		ENST00000336915.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SKAP1	ENST00000336915.11	c.280+11767T>C		intron_variant		1	NM_003726.4	P1

Frequencies

GnomAD3 genomes AF: 0.334 AC: 50565 AN: 151556 Hom.: 9125 Cov.: 32

Gnomad AFR AF: 0.469

Gnomad AMI AF: 0.312

Gnomad AMR AF: 0.390

Gnomad ASJ AF: 0.298

Gnomad EAS AF: 0.178

Gnomad SAS AF: 0.187

Gnomad FIN AF: 0.267

Gnomad MID AF: 0.269

Gnomad NFE AF: 0.274

Gnomad OTH AF: 0.319

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.334 AC: 50601 AN: 151674 Hom.: 9134 Cov.: 32 AF XY: 0.330 AC XY: 24483 AN XY: 74094

Gnomad4 AFR AF: 0.469

Gnomad4 AMR AF: 0.390

Gnomad4 ASJ AF: 0.298

Gnomad4 EAS AF: 0.177

Gnomad4 SAS AF: 0.187

Gnomad4 FIN AF: 0.267

Gnomad4 NFE AF: 0.274

Gnomad4 OTH AF: 0.314

Alfa AF: 0.273 Hom.: 7307

Bravo AF: 0.354

Asia WGS AF: 0.221 AC: 769 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	6.7
Dann	Benign	0.74

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: rs9303542; hg19: chr17-46411500;