Variant 17-48137250-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_003726.4(SKAP1):c.1066G>A(p.Val356Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,460,960 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: 0.0000014 ( 0 hom. )

Consequence

SKAP1
NM_003726.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -2.19

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 Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.01780495).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
SKAP1	NM_003726.4 linkuse as main transcript	c.1066G>A	p.Val356Met	missense_variant	12/13	ENST00000336915.11	NP_003717.3
SKAP1	NM_001075099.2 linkuse as main transcript	c.1063G>A	p.Val355Met	missense_variant	12/13		NP_001068567.1
SKAP1	XM_005257755.5 linkuse as main transcript	c.1012G>A	p.Val338Met	missense_variant	11/12		XP_005257812.1
SKAP1	XM_017025258.2 linkuse as main transcript	c.799G>A	p.Val267Met	missense_variant	9/10		XP_016880747.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SKAP1	ENST00000336915.11 linkuse as main transcript	c.1066G>A	p.Val356Met	missense_variant	12/13	1	NM_003726.4	ENSP00000338171	P1	Q86WV1-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1460960

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

726834

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.00e-7

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

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

Jul 14, 2022

The c.1066G>A (p.V356M) alteration is located in exon 12 (coding exon 12) of the SKAP1 gene. This alteration results from a G to A substitution at nucleotide position 1066, causing the valine (V) at amino acid position 356 to be replaced by a methionine (M). 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

0.081

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.72

CADD

Benign

0.67

DANN

Benign

0.56

DEOGEN2

Benign

0.091

T;T

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.020

LIST_S2

Benign

0.63

.;T

M_CAP

Benign

0.0082

MetaRNN

Benign

0.018

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.29

N;N

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.30

PROVEAN

Benign

-0.42

N;.

REVEL

Benign

0.0020

Sift

Benign

0.18

T;.

Sift4G

Benign

0.22

T;T

Polyphen

0.0010

B;B

Vest4

0.076

MutPred

0.19

Gain of disorder (P = 0.0989);Gain of disorder (P = 0.0989);

MVP

0.17

MPC

0.20

ClinPred

0.041

GERP RS

-8.4

Varity_R

0.024

gMVP

0.25

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over