1-2306689-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_003036.4(SKI):​c.2111A>T​(p.Glu704Val) variant causes a missense change. The variant allele was found at a frequency of 0.000000718 in 1,391,860 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E704G) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 7.2e-7 ( 0 hom. )

Consequence

SKI
NM_003036.4 missense

Scores

3
12
4

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.80
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SKINM_003036.4 linkc.2111A>T p.Glu704Val missense_variant Exon 7 of 7 ENST00000378536.5 NP_003027.1 P12755

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SKIENST00000378536.5 linkc.2111A>T p.Glu704Val missense_variant Exon 7 of 7 1 NM_003036.4 ENSP00000367797.4 P12755

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
7.18e-7
AC:
1
AN:
1391860
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
686546
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:
9.28e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.25
BayesDel_addAF
Pathogenic
0.21
D
BayesDel_noAF
Uncertain
0.060
CADD
Benign
23
DANN
Uncertain
0.99
DEOGEN2
Uncertain
0.76
D
Eigen
Benign
0.11
Eigen_PC
Benign
0.11
FATHMM_MKL
Uncertain
0.92
D
LIST_S2
Uncertain
0.91
D
M_CAP
Pathogenic
0.84
D
MetaRNN
Uncertain
0.43
T
MetaSVM
Uncertain
0.49
D
MutationAssessor
Uncertain
2.5
M
PrimateAI
Pathogenic
0.91
D
PROVEAN
Uncertain
-4.0
D
REVEL
Uncertain
0.57
Sift
Uncertain
0.0010
D
Sift4G
Uncertain
0.0030
D
Polyphen
0.61
P
Vest4
0.34
MutPred
0.15
Gain of methylation at K703 (P = 0.0413);
MVP
0.91
MPC
1.8
ClinPred
1.0
D
GERP RS
1.9
Varity_R
0.33
gMVP
0.52

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-2238128; API