rs75280988

Variant names:

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_003036.4(SKI):c.1163C>T(p.Ala388Val) variant causes a missense change. The variant allele was found at a frequency of 0.00567 in 1,613,740 control chromosomes in the GnomAD database, including 44 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 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. A388T) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0040 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0058 ( 43 hom. )

Consequence

SKI
NM_003036.4 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:13

Conservation

PhyloP100: 5.38

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.008442789).

BP6

Variant 1-2303352-C-T is Benign according to our data. Variant chr1-2303352-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 213668.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-2303352-C-T is described in Lovd as [Likely_benign]. Variant chr1-2303352-C-T is described in Lovd as [Benign].

BS2

High AC in GnomAd4 at 610 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SKI	NM_003036.4 link	c.1163C>T	p.Ala388Val	missense_variant	Exon 3 of 7	ENST00000378536.5	NP_003027.1	P12755

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
SKI	ENST00000378536.5 link	c.1163C>T	p.Ala388Val	missense_variant	Exon 3 of 7	1	NM_003036.4	ENSP00000367797.4	P12755
SKI	ENST00000478223.2 link	n.270C>T		non_coding_transcript_exon_variant	Exon 3 of 3	3
SKI	ENST00000704337.1 link	n.331C>T		non_coding_transcript_exon_variant	Exon 3 of 4

Frequencies

GnomAD3 genomes

AF:

0.00401

AC:

611

AN:

152180

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00111

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00739

Gnomad ASJ

AF:

0.0144

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.000377

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.00566

Gnomad OTH

AF:

0.00384

GnomAD3 exomes

AF:

0.00427

AC:

1073

AN:

251244

Hom.:

AF XY:

0.00429

AC XY:

583

AN XY:

135818

show subpopulations

Gnomad AFR exome

AF:

0.00105

Gnomad AMR exome

AF:

0.00411

Gnomad ASJ exome

AF:

0.0136

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.000327

Gnomad FIN exome

AF:

0.000418

Gnomad NFE exome

AF:

0.00628

Gnomad OTH exome

AF:

0.00685

GnomAD4 exome

AF:

0.00585

AC:

8545

AN:

1461442

Hom.:

Cov.:

AF XY:

0.00560

AC XY:

4071

AN XY:

727040

show subpopulations

Gnomad4 AFR exome

AF:

0.00131

Gnomad4 AMR exome

AF:

0.00449

Gnomad4 ASJ exome

AF:

0.0145

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.000278

Gnomad4 FIN exome

AF:

0.000887

Gnomad4 NFE exome

AF:

0.00669

Gnomad4 OTH exome

AF:

0.00656

GnomAD4 genome

AF:

0.00401

AC:

610

AN:

152298

Hom.:

Cov.:

AF XY:

0.00375

AC XY:

279

AN XY:

74474

show subpopulations

Gnomad4 AFR

AF:

0.00108

Gnomad4 AMR

AF:

0.00738

Gnomad4 ASJ

AF:

0.0144

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.000377

Gnomad4 NFE

AF:

0.00566

Gnomad4 OTH

AF:

0.00380

Alfa

AF:

0.00591

Hom.:

Bravo

AF:

0.00482

TwinsUK

AF:

0.00620

AC:

ALSPAC

AF:

0.00727

AC:

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.00593

AC:

ExAC

AF:

0.00384

AC:

466

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:13

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:5

Jan 26, 2017

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Mar 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

SKI: BS2 -

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

not specified

Benign:4

Aug 19, 2016

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jul 29, 2023

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Shprintzen-Goldberg syndrome

Benign:3

Nov 11, 2024

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

May 28, 2019

Mendelics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Familial thoracic aortic aneurysm and aortic dissection

Benign:1

Jul 17, 2017

Ambry Genetics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, 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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.080

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.23

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.28

Eigen

Benign

-0.75

Eigen_PC

Benign

-0.76

FATHMM_MKL

Benign

0.72

LIST_S2

Benign

0.81

M_CAP

Uncertain

0.19

MetaRNN

Benign

0.0084

MetaSVM

Benign

-0.30

MutationAssessor

Benign

1.2

PrimateAI

Benign

0.44

PROVEAN

Benign

-0.99

REVEL

Benign

0.24

Sift

Benign

0.30

Sift4G

Benign

0.29

Polyphen

0.38

Vest4

0.35

MVP

0.57

MPC

0.20

ClinPred

0.0075

GERP RS

3.1

Varity_R

0.021

gMVP

0.32

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over