rs28384811

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_003036.4(SKI):c.185C>G(p.Ala62Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0703 in 1,396,788 control chromosomes in the GnomAD database, including 3,804 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 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. A62S) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.053 ( 290 hom., cov: 32)

Exomes 𝑓: 0.072 ( 3514 hom. )

Consequence

SKI
NM_003036.4 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.59

Publications

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

SKI links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript NM_003036.4, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0017156601).

BP6

Variant 1-2228951-C-G is Benign according to our data. Variant chr1-2228951-C-G is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 139113.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0702 is higher than 0.05.

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.185C>G	p.Ala62Gly	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.185C>G	p.Ala62Gly	missense	Exon 1 of 7	ENSP00000367797.4	P12755
SKI	ENST00000851187.1		c.185C>G	p.Ala62Gly	missense	Exon 1 of 7	ENSP00000521247.1
SKI	ENST00000704337.1		n.137+1427C>G		intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.0533

AC:

8011

AN:

150266

Hom.:

290

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0298

Gnomad AMI

AF:

0.0198

Gnomad AMR

AF:

0.0576

Gnomad ASJ

AF:

0.0949

Gnomad EAS

AF:

0.00605

Gnomad SAS

AF:

0.0760

Gnomad FIN

AF:

0.0318

Gnomad MID

AF:

0.151

Gnomad NFE

AF:

0.0693

Gnomad OTH

AF:

0.0687

GnomAD2 exomes

AF:

0.0877

AC:

4816

AN:

54924

AF XY:

0.0899

show subpopulations

Gnomad AFR exome

AF:

0.0347

Gnomad AMR exome

AF:

0.0680

Gnomad ASJ exome

AF:

0.107

Gnomad EAS exome

AF:

0.0124

Gnomad FIN exome

AF:

0.0415

Gnomad NFE exome

AF:

0.0920

Gnomad OTH exome

AF:

0.103

GnomAD4 exome

AF:

0.0724

AC:

90238

AN:

1246414

Hom.:

3514

Cov.:

AF XY:

0.0737

AC XY:

45257

AN XY:

614398

show subpopulations

African (AFR)

AF:

0.0281

AC:

690

AN:

24576

American (AMR)

AF:

0.0618

AC:

1059

AN:

17130

Ashkenazi Jewish (ASJ)

AF:

0.101

AC:

2009

AN:

19902

East Asian (EAS)

AF:

0.00432

AC:

113

AN:

26160

South Asian (SAS)

AF:

0.0915

AC:

5762

AN:

62994

European-Finnish (FIN)

AF:

0.0414

AC:

1299

AN:

31392

Middle Eastern (MID)

AF:

0.123

AC:

476

AN:

3862

European-Non Finnish (NFE)

AF:

0.0744

AC:

75165

AN:

1010124

Other (OTH)

AF:

0.0729

AC:

3665

AN:

50274

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.515

Heterozygous variant carriers

4150

8300

12450

16600

20750

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2908

5816

8724

11632

14540

<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

AF:

0.0533

AC:

8009

AN:

150374

Hom.:

290

Cov.:

AF XY:

0.0510

AC XY:

3746

AN XY:

73436

show subpopulations

African (AFR)

AF:

0.0297

AC:

1228

AN:

41338

American (AMR)

AF:

0.0574

AC:

869

AN:

15132

Ashkenazi Jewish (ASJ)

AF:

0.0949

AC:

326

AN:

3436

East Asian (EAS)

AF:

0.00607

AC:

AN:

5110

South Asian (SAS)

AF:

0.0767

AC:

370

AN:

4826

European-Finnish (FIN)

AF:

0.0318

AC:

316

AN:

9922

Middle Eastern (MID)

AF:

0.152

AC:

AN:

290

European-Non Finnish (NFE)

AF:

0.0693

AC:

4665

AN:

67320

Other (OTH)

AF:

0.0679

AC:

142

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

378

755

1133

1510

1888

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

200

300

400

500

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0583

Hom.:

Bravo

AF:

0.0544

Asia WGS

AF:

0.0290

AC:

100

AN:

3426

ClinVar

ClinVar submissions

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (6)

not provided (3)

Shprintzen-Goldberg syndrome (3)

Familial thoracic aortic aneurysm and aortic dissection (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.088

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.14

CADD

Benign

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.21

Eigen

Benign

-0.037

Eigen_PC

Benign

-0.050

FATHMM_MKL

Benign

0.73

LIST_S2

Benign

0.60

MetaRNN

Benign

0.0017

MetaSVM

Benign

-0.30

MutationAssessor

Benign

0.0

PhyloP100

1.6

PrimateAI

Pathogenic

0.87

PROVEAN

Benign

-0.14

REVEL

Benign

0.20

Sift

Uncertain

0.017

Sift4G

Benign

0.47

Varity_R

0.074

gMVP

0.39

Mutation Taster

=99/1

polymorphism (auto)

(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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over