17-48184809-C-T

Variant names:

• chr17-48184809-C-T
• rs2278868
• NM_003726.4:c.481G>A

Variant summary

Our verdict is Benign. The variant received -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. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• 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
• Publications: 53 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 (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 rank	MANE	Protein	UniProt
SKAP1	NM_003726.4	c.481G>A	p.Gly161Ser	missense_variant	Exon 7 of 13	ENST00000336915.11	NP_003717.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SKAP1	ENST00000336915.11	c.481G>A	p.Gly161Ser	missense_variant	Exon 7 of 13	1	NM_003726.4	ENSP00000338171.6

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

GnomAD2 exomes AF: 0.628 AC: 157757 AN: 251082 AF XY: 0.632

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 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

African (AFR) AF: 0.376 AC: 12566 AN: 33458

American (AMR) AF: 0.710 AC: 31738 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.577 AC: 15069 AN: 26130

East Asian (EAS) AF: 0.776 AC: 30791 AN: 39688

South Asian (SAS) AF: 0.707 AC: 60989 AN: 86240

European-Finnish (FIN) AF: 0.617 AC: 32960 AN: 53408

Middle Eastern (MID) AF: 0.488 AC: 2805 AN: 5752

European-Non Finnish (NFE) AF: 0.608 AC: 675453 AN: 1111518

Other (OTH) AF: 0.606 AC: 36584 AN: 60366

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

African (AFR) AF: 0.392 AC: 16230 AN: 41406

American (AMR) AF: 0.654 AC: 10000 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.578 AC: 2004 AN: 3470

East Asian (EAS) AF: 0.768 AC: 3953 AN: 5150

South Asian (SAS) AF: 0.726 AC: 3501 AN: 4824

European-Finnish (FIN) AF: 0.619 AC: 6532 AN: 10552

Middle Eastern (MID) AF: 0.527 AC: 154 AN: 292

European-Non Finnish (NFE) AF: 0.600 AC: 40751 AN: 67930

Other (OTH) AF: 0.579 AC: 1221 AN: 2108

Alfa AF: 0.587 Hom.: 89536

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
PhyloP100		1.3
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
PromoterAI		-0.025	Neutral
Varity_R		0.031
gMVP		0.13
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2278868; hg19: chr17-46262171; COSMIC: COSV61146844; COSMIC: COSV61146844;