Genetic Variant SKI:p.Ala5Gly (chr1-2228780-C-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_003036.4(SKI):c.14C>G(p.Ala5Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A5T) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

SKI
NM_003036.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.12

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, Labcorp Genetics (formerly Invitae), PanelApp Australia, G2P, Orphanet, Genomics England PanelApp, ClinGen

SKI links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.2049526).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003036.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SKI	NM_003036.4	MANE Select	c.14C>G	p.Ala5Gly	missense	Exon 1 of 7	NP_003027.1	P12755

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SKI	ENST00000378536.5	TSL:1 MANE Select	c.14C>G	p.Ala5Gly	missense	Exon 1 of 7	ENSP00000367797.4	P12755
SKI	ENST00000851187.1		c.14C>G	p.Ala5Gly	missense	Exon 1 of 7	ENSP00000521247.1
SKI	ENST00000704337.1		n.137+1256C>G		intron	N/A

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1143546

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

560868

African (AFR)

AF:

0.00

AC:

AN:

23160

American (AMR)

AF:

0.00

AC:

AN:

21338

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

17412

East Asian (EAS)

AF:

0.00

AC:

AN:

19156

South Asian (SAS)

AF:

0.00

AC:

AN:

55172

European-Finnish (FIN)

AF:

0.00

AC:

AN:

22050

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3042

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

939004

Other (OTH)

AF:

0.00

AC:

AN:

43212

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Familial thoracic aortic aneurysm and aortic dissection (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.059

BayesDel_addAF

Benign

-0.010

BayesDel_noAF

Benign

-0.25

CADD

Benign

(source)

DANN

Benign

0.93

DEOGEN2

Benign

0.24

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.31

LIST_S2

Benign

0.50

M_CAP

Pathogenic

0.91

MetaRNN

Benign

0.20

MetaSVM

Benign

-0.38

MutationAssessor

Benign

0.55

PhyloP100

3.1

PrimateAI

Pathogenic

0.87

PROVEAN

Benign

-0.92

REVEL

Benign

0.22

Sift

Benign

0.42

Sift4G

Uncertain

0.057

Polyphen

0.0

Vest4

0.26

MutPred

0.24

Gain of loop (P = 0.0851)

MVP

0.51

MPC

2.0

ClinPred

0.27

GERP RS

-1.4

PromoterAI

0.0088

Neutral

(source)

RBP_binding_hub_radar

1.1

RBP_regulation_power_radar

2.9

Varity_R

0.070

gMVP

0.19

Mutation Taster

=93/7

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over