rs9894812

Variant names:

• chr17-48312591-T-C
• rs9894812
• NM_003726.4:c.280+33314A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003726.4(SKAP1):​c.280+33314A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.338 in 152,106 control chromosomes in the GnomAD database, including 9,451 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 0.34 (9451 hom., cov: 32)
• Consequence: SKAP1 NM_003726.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0290
• Publications: 8 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.65).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.477 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003726.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SKAP1	NM_003726.4	MANE Select	c.280+33314A>G		intron	N/A	NP_003717.3
	SKAP1	NM_001075099.2		c.280+33314A>G		intron	N/A	NP_001068567.1	Q86WV1-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SKAP1	ENST00000336915.11	TSL:1 MANE Select	c.280+33314A>G		intron	N/A	ENSP00000338171.6	Q86WV1-1
	SKAP1	ENST00000970118.1		c.280+33314A>G		intron	N/A	ENSP00000640177.1
	SKAP1	ENST00000584924.5	TSL:2	c.280+33314A>G		intron	N/A	ENSP00000464311.1	Q86WV1-1

Frequencies

GnomAD3 genomes AF: 0.338 AC: 51316 AN: 151988 Hom.: 9441 Cov.: 32

Gnomad AFR AF: 0.483

Gnomad AMI AF: 0.309

Gnomad AMR AF: 0.391

Gnomad ASJ AF: 0.299

Gnomad EAS AF: 0.177

Gnomad SAS AF: 0.186

Gnomad FIN AF: 0.267

Gnomad MID AF: 0.269

Gnomad NFE AF: 0.274

Gnomad OTH AF: 0.320

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

GnomAD4 genome AF: 0.338 AC: 51353 AN: 152106 Hom.: 9451 Cov.: 32 AF XY: 0.334 AC XY: 24860 AN XY: 74370

African (AFR) AF: 0.483 AC: 20034 AN: 41478

American (AMR) AF: 0.392 AC: 5995 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.299 AC: 1037 AN: 3472

East Asian (EAS) AF: 0.176 AC: 912 AN: 5174

South Asian (SAS) AF: 0.186 AC: 896 AN: 4822

European-Finnish (FIN) AF: 0.267 AC: 2822 AN: 10582

Middle Eastern (MID) AF: 0.262 AC: 77 AN: 294

European-Non Finnish (NFE) AF: 0.274 AC: 18634 AN: 67968

Other (OTH) AF: 0.315 AC: 665 AN: 2110

Alfa AF: 0.295 Hom.: 3563

Bravo AF: 0.358

Asia WGS AF: 0.222 AC: 776 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
CADD	Benign	14
DANN	Benign	0.73
PhyloP100		0.029
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs9894812; hg19: chr17-46389953;