GeneBe

1-2304438-G-T

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2BP4_StrongBP7

The NM_003036.4(SKI):​c.1620G>T​(p.Ala540Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000071 in 1,408,786 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. A540A) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 7.1e-7 ( 0 hom. )

Consequence

SKI
NM_003036.4 synonymous

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.58

Publications

0 publications found
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]
SKI Gene-Disease associations (from GenCC):
  • Shprintzen-Goldberg syndrome
    Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Ambry Genetics, PanelApp Australia, G2P, Genomics England PanelApp, ClinGen, Orphanet, Labcorp Genetics (formerly Invitae)

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.61).
BP7
Synonymous conserved (PhyloP=-2.58 with no splicing effect.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SKINM_003036.4 linkc.1620G>T p.Ala540Ala synonymous_variant Exon 5 of 7 ENST00000378536.5 NP_003027.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SKIENST00000378536.5 linkc.1620G>T p.Ala540Ala synonymous_variant Exon 5 of 7 1 NM_003036.4 ENSP00000367797.4
SKIENST00000507179.1 linkn.*70G>T downstream_gene_variant 2

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
7.10e-7
AC:
1
AN:
1408786
Hom.:
0
Cov.:
34
AF XY:
0.00000144
AC XY:
1
AN XY:
696370
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
31906
American (AMR)
AF:
0.00
AC:
0
AN:
37406
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
25262
East Asian (EAS)
AF:
0.00
AC:
0
AN:
36266
South Asian (SAS)
AF:
0.00
AC:
0
AN:
80024
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
48140
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5710
European-Non Finnish (NFE)
AF:
9.21e-7
AC:
1
AN:
1085680
Other (OTH)
AF:
0.00
AC:
0
AN:
58392
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.525
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
Cov.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.61
CADD
Benign
0.88
DANN
Benign
0.61
PhyloP100
-2.6
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
2.9
Mutation Taster
=100/0
polymorphism

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

dbSNP: rs529842293; hg19: chr1-2235877; COSMIC: COSV66012795; COSMIC: COSV66012795; API