17-48184809-C-T

Position:

• chr17-48184809-C-T

Variant summary

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

The NM_003726.4(SKAP1):​c.481G>A​(p.Gly161Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.61 in 1,613,196 control chromosomes in the GnomAD database, including 304,030 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.56 (24697 hom., cov: 31)
  • Exomes 𝑓: 0.62 (279333 hom.)
• Consequence: SKAP1 NM_003726.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.31

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 (MetaRNN=1.5825706E-5).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.748 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SKAP1	NM_003726.4	c.481G>A	p.Gly161Ser	missense_variant	7/13	ENST00000336915.11	NP_003717.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SKAP1	ENST00000336915.11	c.481G>A	p.Gly161Ser	missense_variant	7/13	1	NM_003726.4	ENSP00000338171	P1

Frequencies

GnomAD3 genomes AF: 0.559 AC: 84797 AN: 151808 Hom.: 24671 Cov.: 31

Gnomad AFR AF: 0.392

Gnomad AMI AF: 0.571

Gnomad AMR AF: 0.654

Gnomad ASJ AF: 0.578

Gnomad EAS AF: 0.768

Gnomad SAS AF: 0.726

Gnomad FIN AF: 0.619

Gnomad MID AF: 0.522

Gnomad NFE AF: 0.600

Gnomad OTH AF: 0.577

GnomAD3 exomes AF: 0.628 AC: 157757 AN: 251082 Hom.: 50784 AF XY: 0.632 AC XY: 85727 AN XY: 135720

Gnomad AFR exome AF: 0.385

Gnomad AMR exome AF: 0.720

Gnomad ASJ exome AF: 0.573

Gnomad EAS exome AF: 0.757

Gnomad SAS exome AF: 0.713

Gnomad FIN exome AF: 0.618

Gnomad NFE exome AF: 0.600

Gnomad OTH exome AF: 0.610

GnomAD4 exome AF: 0.615 AC: 898955 AN: 1461270 Hom.: 279333 Cov.: 41 AF XY: 0.618 AC XY: 448932 AN XY: 726990

Gnomad4 AFR exome AF: 0.376

Gnomad4 AMR exome AF: 0.710

Gnomad4 ASJ exome AF: 0.577

Gnomad4 EAS exome AF: 0.776

Gnomad4 SAS exome AF: 0.707

Gnomad4 FIN exome AF: 0.617

Gnomad4 NFE exome AF: 0.608

Gnomad4 OTH exome AF: 0.606

GnomAD4 genome AF: 0.559 AC: 84867 AN: 151926 Hom.: 24697 Cov.: 31 AF XY: 0.568 AC XY: 42178 AN XY: 74254

Gnomad4 AFR AF: 0.392

Gnomad4 AMR AF: 0.654

Gnomad4 ASJ AF: 0.578

Gnomad4 EAS AF: 0.768

Gnomad4 SAS AF: 0.726

Gnomad4 FIN AF: 0.619

Gnomad4 NFE AF: 0.600

Gnomad4 OTH AF: 0.579

Alfa AF: 0.594 Hom.: 67064

Bravo AF: 0.552

TwinsUK AF: 0.609 AC: 2258

ALSPAC AF: 0.600 AC: 2312

ESP6500AA AF: 0.398 AC: 1754

ESP6500EA AF: 0.603 AC: 5189

ExAC AF: 0.622 AC: 75551

Asia WGS AF: 0.752 AC: 2615 AN: 3478

EpiCase AF: 0.588

EpiControl AF: 0.594

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.048
BayesDel_addAF	Benign	-0.63	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	15
DANN	Benign	0.82
DEOGEN2	Benign	0.17	T;T
Eigen	Benign	-0.90
Eigen_PC	Benign	-0.57
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.10	.;T
MetaRNN	Benign	0.000016	T;T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	-1.9	N;N
MutationTaster	Benign	1.0	P;P
PrimateAI	Benign	0.39	T
PROVEAN	Benign	1.9	N;.
REVEL	Benign	0.14
Sift	Benign	1.0	T;.
Sift4G	Benign	1.0	T;T
Polyphen		0.0	B;B
Vest4		0.038
MPC		0.20
ClinPred		0.0044	T
GERP RS		5.4
Varity_R		0.031
gMVP		0.13

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs2278868; hg19: chr17-46262171; COSMIC: COSV61146844; COSMIC: COSV61146844;