rs387907305
Variant summary
Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PM1PM5PP3_ModeratePP5_Moderate
The NM_003036.4(SKI):c.101G>A(p.Gly34Asp) variant causes a missense change involving the alteration of a conserved nucleotide. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G34C) has been classified as Pathogenic.
Frequency
Genomes: not found (cov: 31)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
SKI
NM_003036.4 missense
NM_003036.4 missense
Scores
12
4
3
Clinical Significance
Conservation
PhyloP100: 8.34
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]
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ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 8 ACMG points.
PM1
?
In a hotspot region, there are 5 aminoacids with missense pathogenic changes in the window of +-8 aminoacids around while only 0 benign, 5 uncertain in NM_003036.4
PM5
?
Other missense variant is known to change same aminoacid residue: Variant chr1-2228866-G-T is described in ClinVar as [Pathogenic]. Clinvar id is 37262.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.923
PP5
?
Variant 1-2228867-G-A is Pathogenic according to our data. Variant chr1-2228867-G-A is described in ClinVar as [Pathogenic]. Clinvar id is 37260.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-2228867-G-A is described in Lovd as [Likely_pathogenic]. Variant chr1-2228867-G-A is described in Lovd as [Pathogenic].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SKI | NM_003036.4 | c.101G>A | p.Gly34Asp | missense_variant | 1/7 | ENST00000378536.5 | |
SKI | XM_005244775.4 | c.101G>A | p.Gly34Asp | missense_variant | 1/7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SKI | ENST00000378536.5 | c.101G>A | p.Gly34Asp | missense_variant | 1/7 | 1 | NM_003036.4 | P1 | |
SKI | ENST00000704337.1 | n.137+1343G>A | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes ? Cov.: 31
GnomAD3 genomes
?
Cov.:
31
GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 1280926Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 633106
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
AC:
0
AN:
1280926
Hom.:
Cov.:
31
AF XY:
AC XY:
0
AN XY:
633106
Gnomad4 AFR exome
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Gnomad4 AMR exome
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Gnomad4 EAS exome
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Gnomad4 SAS exome
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Gnomad4 FIN exome
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Gnomad4 OTH exome
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GnomAD4 genome ? Cov.: 31
GnomAD4 genome
?
Cov.:
31
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:2
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Shprintzen-Goldberg syndrome Pathogenic:2
Pathogenic, no assertion criteria provided | literature only | OMIM | Feb 01, 2015 | - - |
Pathogenic, criteria provided, single submitter | research | Baylor-Hopkins Center for Mendelian Genomics, Johns Hopkins University School of Medicine | - | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
Cadd
Pathogenic
Dann
Uncertain
DEOGEN2
Pathogenic
D
Eigen
Uncertain
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D
M_CAP
Pathogenic
D
MetaRNN
Pathogenic
D
MetaSVM
Pathogenic
D
MutationAssessor
Benign
L
MutationTaster
Benign
D
PrimateAI
Pathogenic
D
PROVEAN
Pathogenic
D
REVEL
Pathogenic
Sift
Pathogenic
D
Sift4G
Pathogenic
D
Polyphen
D
Vest4
MutPred
Loss of catalytic residue at G34 (P = 0.0123);
MVP
MPC
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at