17-48180074-T-C

Position:

• chr17-48180074-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_003726.4(SKAP1):​c.806A>G​(p.Asp269Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
• Consequence: SKAP1 NM_003726.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.91

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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SKAP1	NM_003726.4	c.806A>G	p.Asp269Gly	missense_variant	9/13	ENST00000336915.11	NP_003717.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SKAP1	ENST00000336915.11	c.806A>G	p.Asp269Gly	missense_variant	9/13	1	NM_003726.4	ENSP00000338171.6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 20, 2024

The c.806A>G (p.D269G) alteration is located in exon 9 (coding exon 9) of the SKAP1 gene. This alteration results from a A to G substitution at nucleotide position 806, causing the aspartic acid (D) at amino acid position 269 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.48	T;T
Eigen	Benign	0.026
Eigen_PC	Benign	-0.045
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Benign	0.70	.;T
M_CAP	Benign	0.0052	T
MetaRNN	Benign	0.14	T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Uncertain	2.7	M;M
PrimateAI	Benign	0.33	T
PROVEAN	Pathogenic	-5.0	D;.
REVEL	Benign	0.075
Sift	Uncertain	0.022	D;.
Sift4G	Uncertain	0.0030	D;D
Polyphen		0.11	B;B
Vest4		0.15
MutPred		0.28		Loss of stability (P = 0.085);Loss of stability (P = 0.085);
MVP		0.39
MPC		0.29
ClinPred		0.97	D
GERP RS		1.9
Varity_R		0.59
gMVP		0.44

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.43		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.43		Position offset: 1

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-46257436;