chr17-48162497-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_003726.4(SKAP1):​c.950G>A​(p.Arg317Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000223 in 1,613,858 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000022 ( 0 hom. )

Consequence

SKAP1
NM_003726.4 missense

Scores

5
7
7

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.49
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.767

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
SKAP1NM_003726.4 linkuse as main transcriptc.950G>A p.Arg317Gln missense_variant 11/13 ENST00000336915.11 NP_003717.3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
SKAP1ENST00000336915.11 linkuse as main transcriptc.950G>A p.Arg317Gln missense_variant 11/131 NM_003726.4 ENSP00000338171 P1Q86WV1-1

Frequencies

GnomAD3 genomes
AF:
0.0000263
AC:
4
AN:
152172
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000441
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000318
AC:
8
AN:
251250
Hom.:
0
AF XY:
0.0000295
AC XY:
4
AN XY:
135774
show subpopulations
Gnomad AFR exome
AF:
0.0000616
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000981
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000264
Gnomad OTH exome
AF:
0.000163
GnomAD4 exome
AF:
0.0000219
AC:
32
AN:
1461686
Hom.:
0
Cov.:
30
AF XY:
0.0000206
AC XY:
15
AN XY:
727142
show subpopulations
Gnomad4 AFR exome
AF:
0.000149
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000232
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000180
Gnomad4 OTH exome
AF:
0.0000662
GnomAD4 genome
AF:
0.0000263
AC:
4
AN:
152172
Hom.:
0
Cov.:
32
AF XY:
0.0000269
AC XY:
2
AN XY:
74330
show subpopulations
Gnomad4 AFR
AF:
0.0000241
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000441
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000434
Hom.:
0
Bravo
AF:
0.0000113
ExAC
AF:
0.0000247
AC:
3
Asia WGS
AF:
0.000577
AC:
2
AN:
3478
EpiCase
AF:
0.000109
EpiControl
AF:
0.00

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 submitterclinical testingAmbry GeneticsSep 20, 2023The c.950G>A (p.R317Q) alteration is located in exon 11 (coding exon 11) of the SKAP1 gene. This alteration results from a G to A substitution at nucleotide position 950, causing the arginine (R) at amino acid position 317 to be replaced by a glutamine (Q). 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
Uncertain
0.39
BayesDel_addAF
Benign
-0.055
T
BayesDel_noAF
Benign
-0.11
CADD
Pathogenic
30
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.29
T;T
Eigen
Pathogenic
0.74
Eigen_PC
Pathogenic
0.77
FATHMM_MKL
Uncertain
0.93
D
LIST_S2
Pathogenic
0.98
.;D
M_CAP
Benign
0.021
T
MetaRNN
Pathogenic
0.77
D;D
MetaSVM
Benign
-0.72
T
MutationAssessor
Benign
0.81
L;L
MutationTaster
Benign
1.0
D;D
PrimateAI
Uncertain
0.56
T
PROVEAN
Uncertain
-3.2
D;.
REVEL
Uncertain
0.33
Sift
Uncertain
0.0030
D;.
Sift4G
Uncertain
0.0060
D;D
Polyphen
1.0
D;D
Vest4
0.85
MutPred
0.51
Gain of disorder (P = 0.1454);Gain of disorder (P = 0.1454);
MVP
0.74
MPC
0.83
ClinPred
0.74
D
GERP RS
5.8
Varity_R
0.56
gMVP
0.68

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.16
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.

Other links and lift over

dbSNP: rs368166369; hg19: chr17-46239859; COSMIC: COSV104636399; API