Variant 17-48137296-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_003726.4(SKAP1):c.1020C>G(p.Ser340Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000547 in 1,461,536 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000055 ( 0 hom. )

Consequence

SKAP1
NM_003726.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.28

Variant links:

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]

SKAP1 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.19160044).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
SKAP1	NM_003726.4 linkuse as main transcript	c.1020C>G	p.Ser340Arg	missense_variant	12/13	ENST00000336915.11
SKAP1	NM_001075099.2 linkuse as main transcript	c.1017C>G	p.Ser339Arg	missense_variant	12/13
SKAP1	XM_005257755.5 linkuse as main transcript	c.966C>G	p.Ser322Arg	missense_variant	11/12
SKAP1	XM_017025258.2 linkuse as main transcript	c.753C>G	p.Ser251Arg	missense_variant	9/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SKAP1	ENST00000336915.11 linkuse as main transcript	c.1020C>G	p.Ser340Arg	missense_variant	12/13	1	NM_003726.4	P1	Q86WV1-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000358

AC:

AN:

251200

Hom.:

AF XY:

0.0000516

AC XY:

AN XY:

135760

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000489

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000547

AC:

AN:

1461536

Hom.:

Cov.:

AF XY:

0.00000688

AC XY:

AN XY:

727092

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000176

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000756

ExAC

AF:

0.0000330

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 11, 2023

The c.1020C>G (p.S340R) alteration is located in exon 12 (coding exon 12) of the SKAP1 gene. This alteration results from a C to G substitution at nucleotide position 1020, causing the serine (S) at amino acid position 340 to be replaced by an arginine (R). 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

0.32

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.32

Cadd

Benign

Dann

Uncertain

1.0

DEOGEN2

Benign

0.17

T;T

Eigen

Benign

0.059

Eigen_PC

Benign

0.098

FATHMM_MKL

Benign

0.74

M_CAP

Benign

0.023

MetaRNN

Benign

0.19

T;T

MetaSVM

Benign

-0.94

MutationAssessor

Benign

0.85

L;L

MutationTaster

Benign

0.87

N;N

PrimateAI

Benign

0.42

PROVEAN

Benign

-2.2

N;.

REVEL

Benign

0.21

Sift

Uncertain

0.0020

D;.

Sift4G

Uncertain

0.0060

D;D

Polyphen

0.93

P;P

Vest4

0.45

MutPred

0.77

Gain of MoRF binding (P = 0.0472);Gain of MoRF binding (P = 0.0472);

MVP

0.64

MPC

0.60

ClinPred

0.22

GERP RS

3.8

Varity_R

0.30

gMVP

0.57

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over