rs12944592

Variant names:

• chr17-48353043-G-A
• rs12944592
• NM_003726.4:c.179-7037C>T

Variant summary

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

The NM_003726.4(SKAP1):​c.179-7037C>T 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 152,056 control chromosomes in the GnomAD database, including 9,190 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 (9190 hom., cov: 32)
• Consequence: SKAP1 NM_003726.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.830
• Publications: 10 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.464 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SKAP1	NM_003726.4	c.179-7037C>T		intron_variant	Intron 3 of 12	ENST00000336915.11	NP_003717.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SKAP1	ENST00000336915.11	c.179-7037C>T		intron_variant	Intron 3 of 12	1	NM_003726.4	ENSP00000338171.6
SKAP1	ENST00000584924.5	c.179-7037C>T		intron_variant	Intron 3 of 11	2		ENSP00000464311.1
SKAP1	ENST00000584709.6	n.179-7037C>T		intron_variant	Intron 3 of 13	2		ENSP00000463284.1

Frequencies

GnomAD3 genomes AF: 0.334 AC: 50748 AN: 151938 Hom.: 9181 Cov.: 32

Gnomad AFR AF: 0.470

Gnomad AMI AF: 0.311

Gnomad AMR AF: 0.390

Gnomad ASJ AF: 0.299

Gnomad EAS AF: 0.179

Gnomad SAS AF: 0.185

Gnomad FIN AF: 0.267

Gnomad MID AF: 0.269

Gnomad NFE AF: 0.274

Gnomad OTH AF: 0.318

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

GnomAD4 genome AF: 0.334 AC: 50784 AN: 152056 Hom.: 9190 Cov.: 32 AF XY: 0.331 AC XY: 24605 AN XY: 74344

African (AFR) AF: 0.470 AC: 19471 AN: 41452

American (AMR) AF: 0.391 AC: 5972 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.299 AC: 1037 AN: 3468

East Asian (EAS) AF: 0.178 AC: 921 AN: 5184

South Asian (SAS) AF: 0.186 AC: 893 AN: 4814

European-Finnish (FIN) AF: 0.267 AC: 2822 AN: 10562

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

European-Non Finnish (NFE) AF: 0.274 AC: 18648 AN: 67978

Other (OTH) AF: 0.313 AC: 659 AN: 2108

Alfa AF: 0.292 Hom.: 3209

Bravo AF: 0.354

Asia WGS AF: 0.222 AC: 774 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	5.8
DANN	Benign	0.60
PhyloP100		0.83
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: rs12944592; hg19: chr17-46430405;