rs1553189874

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP3BP6BS2

The NM_003036.4(SKI):c.191_196dupTGCCCG(p.Val64_Pro65dup) variant causes a disruptive inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000999 in 1,401,326 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. A66A) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000010 ( 0 hom. )

Consequence

SKI
NM_003036.4 disruptive_inframe_insertion

Scores

Not classified

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:1

Conservation

PhyloP100: 2.25

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)

SKI links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP3

Nonframeshift variant in repetitive region in NM_003036.4

BP6

Variant 1-2228955-G-GGTGCCC is Benign according to our data. Variant chr1-2228955-G-GGTGCCC is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 409976.

BS2

High AC in GnomAdExome4 at 13 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SKI	NM_003036.4 link	c.191_196dupTGCCCG	p.Val64_Pro65dup	disruptive_inframe_insertion	Exon 1 of 7	ENST00000378536.5	NP_003027.1	P12755
SKI	XM_005244775.4 link	c.191_196dupTGCCCG	p.Val64_Pro65dup	disruptive_inframe_insertion	Exon 1 of 7		XP_005244832.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SKI	ENST00000378536.5 link	c.191_196dupTGCCCG	p.Val64_Pro65dup	disruptive_inframe_insertion	Exon 1 of 7	1	NM_003036.4	ENSP00000367797.4		P12755
SKI	ENST00000704337.1 link	n.137+1433_137+1438dupTGCCCG		intron_variant	Intron 1 of 3

Frequencies

GnomAD3 genomes

AF:

0.00000664

AC:

AN:

150540

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000148

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000186

AC:

AN:

53866

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000630

GnomAD4 exome

AF:

0.0000104

AC:

AN:

1250786

Hom.:

Cov.:

AF XY:

0.00000811

AC XY:

AN XY:

616448

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

24750

American (AMR)

AF:

0.00

AC:

AN:

16716

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

20040

East Asian (EAS)

AF:

0.00

AC:

AN:

26730

South Asian (SAS)

AF:

0.00

AC:

AN:

62800

European-Finnish (FIN)

AF:

0.00

AC:

AN:

31606

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3928

European-Non Finnish (NFE)

AF:

0.0000118

AC:

AN:

1013590

Other (OTH)

AF:

0.0000198

AC:

AN:

50626

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.00000664

AC:

AN:

150540

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

73486

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41266

American (AMR)

AF:

0.00

AC:

AN:

15134

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3448

East Asian (EAS)

AF:

0.00

AC:

AN:

5140

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9990

Middle Eastern (MID)

AF:

0.00

AC:

AN:

312

European-Non Finnish (NFE)

AF:

0.0000148

AC:

AN:

67448

Other (OTH)

AF:

0.00

AC:

AN:

2064

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000756

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:1

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

Shprintzen-Goldberg syndrome

Uncertain:1

Sep 05, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant, c.191_196dup, results in the insertion of 2 amino acid(s) of the SKI protein (p.Val64_Pro65dup), but otherwise preserves the integrity of the reading frame. This variant is present in population databases (no rsID available, gnomAD no frequency). This variant has not been reported in the literature in individuals affected with SKI-related conditions. ClinVar contains an entry for this variant (Variation ID: 409976). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -

not provided

Benign:1

Sep 13, 2019

GeneDx

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

2.3

Mutation Taster

=71/29

polymorphism

(source)

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over