rs398122914

Positions:

• chr1-2229045-GTCCGACCGCTCC-G

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2 PM4 PP3 PP5

The NM_003036.4(SKI):​c.280_291del​(p.Ser94_Ser97del) variant causes a inframe deletion change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars). Synonymous variant affecting the same amino acid position (i.e. S94S) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SKI NM_003036.4 inframe_deletion
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 9.08

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]

ACMG classification

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM4: Nonframeshift variant in NON repetitive region in NM_003036.4.
• PP3: No computational evidence supports a deleterious effect, but strongly conserved according to phyloP
• PP5: Variant 1-2229045-GTCCGACCGCTCC-G is Pathogenic according to our data. Variant chr1-2229045-GTCCGACCGCTCC-G is described in ClinVar as [Pathogenic]. Clinvar id is 39784.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr1-2229045-GTCCGACCGCTCC-G is described in Lovd as [Pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SKI	NM_003036.4	c.280_291del	p.Ser94_Ser97del	inframe_deletion	1/7	ENST00000378536.5
SKI	XM_005244775.4	c.280_291del	p.Ser94_Ser97del	inframe_deletion	1/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SKI	ENST00000378536.5	c.280_291del	p.Ser94_Ser97del	inframe_deletion	1/7	1	NM_003036.4	P1
SKI	ENST00000704337.1	n.137+1522_137+1533del		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Shprintzen-Goldberg syndrome Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Nov 02, 2012

- -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs398122914; hg19: chr1-2160484;