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rs1488554459

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_ModerateBP6_Very_StrongBS2

The NM_003036.4(SKI):c.2165G>A(p.Gly722Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000125 in 1,525,972 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G722V) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

SKI
NM_003036.4 missense

Scores

1
2
16

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.77
Variant links:
Genes affected
SKI (HGNC:10896): (SKI proto-oncogene) This gene encodes the nuclear protooncogene protein homolog of avian sarcoma viral (v-ski) oncogene. It functions as a repressor of TGF-beta signaling, and may play a role in neural tube development and muscle differentiation. [provided by RefSeq, Oct 2009]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.14627597).
BP6
Variant 1-2306743-G-A is Benign according to our data. Variant chr1-2306743-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 934214.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS2
High AC in GnomAdExome at 10 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SKINM_003036.4 linkuse as main transcriptc.2165G>A p.Gly722Asp missense_variant 7/7 ENST00000378536.5

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SKIENST00000378536.5 linkuse as main transcriptc.2165G>A p.Gly722Asp missense_variant 7/71 NM_003036.4 P1

Frequencies

GnomAD3 genomes
AF:
0.0000197
AC:
3
AN:
152060
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000197
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:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000825
AC:
10
AN:
121180
Hom.:
0
AF XY:
0.0000750
AC XY:
5
AN XY:
66694
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000396
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.000271
GnomAD4 exome
AF:
0.0000116
AC:
16
AN:
1373912
Hom.:
0
Cov.:
32
AF XY:
0.0000118
AC XY:
8
AN XY:
677428
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.000351
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000590
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
9.33e-7
Gnomad4 OTH exome
AF:
0.0000176
GnomAD4 genome
AF:
0.0000197
AC:
3
AN:
152060
Hom.:
0
Cov.:
33
AF XY:
0.0000135
AC XY:
1
AN XY:
74294
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.000197
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000436
Hom.:
0
Bravo
AF:
0.0000227

ClinVar

Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

Familial thoracic aortic aneurysm and aortic dissection Benign:1
Likely benign, criteria provided, single submitterclinical testingAmbry GeneticsFeb 16, 2022This alteration is classified as likely benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -
Shprintzen-Goldberg syndrome Benign:1
Likely benign, criteria provided, single submitterclinical testingInvitaeSep 28, 2023- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.084
BayesDel_addAF
Benign
-0.20
T
BayesDel_noAF
Benign
-0.21
Cadd
Benign
18
Dann
Benign
0.86
DEOGEN2
Benign
0.18
T
Eigen
Benign
-0.73
Eigen_PC
Benign
-0.66
FATHMM_MKL
Benign
0.085
N
LIST_S2
Benign
0.59
T
M_CAP
Pathogenic
0.82
D
MetaRNN
Benign
0.15
T
MetaSVM
Uncertain
-0.11
T
MutationAssessor
Benign
1.1
L
MutationTaster
Benign
1.0
N
PrimateAI
Uncertain
0.74
T
PROVEAN
Benign
0.26
N
REVEL
Benign
0.25
Sift
Benign
0.077
T
Sift4G
Benign
0.62
T
Polyphen
0.0
B
Vest4
0.12
MutPred
0.18
Loss of loop (P = 9e-04);
MVP
0.41
MPC
1.4
ClinPred
0.034
T
GERP RS
4.2
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.0
Varity_R
0.066
gMVP
0.29

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.

Other links and lift over

dbSNP: rs1488554459; hg19: chr1-2238182; API