rs762410895

Variant names:

• chr1-2304066-TCGGAGG-T
• rs762410895
• NM_003036.4:c.1445_1450delCGGAGG

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 3P and 4B. PM4 PP3 BS2

The NM_003036.4(SKI):​c.1445_1450delCGGAGG​(p.Ala482_Glu483del) variant causes a disruptive inframe deletion change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000548 in 1,460,300 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★★). Synonymous variant affecting the same amino acid position (i.e. A482A) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000055 (0 hom.)
• Consequence: SKI NM_003036.4 disruptive_inframe_deletion
• Clinical Significance: Uncertain significance criteria provided, multiple submitters, no conflicts U:2
• Conservation: PhyloP100: 9.02
• Publications: 0 publications found

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

ACMG classification

Our verdict: Likely_benign. The variant received -1 ACMG points.

• 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
• BS2: High AC in GnomAdExome4 at 80 AD gene.

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.1445_1450delCGGAGG	p.Ala482_Glu483del	disruptive_inframe_deletion	Exon 4 of 7	NP_003027.1	P12755

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SKI	ENST00000378536.5	TSL:1 MANE Select	c.1445_1450delCGGAGG	p.Ala482_Glu483del	disruptive_inframe_deletion	Exon 4 of 7	ENSP00000367797.4	P12755
	SKI	ENST00000851187.1		c.1445_1450delCGGAGG	p.Ala482_Glu483del	disruptive_inframe_deletion	Exon 4 of 7	ENSP00000521247.1
	SKI	ENST00000507179.1	TSL:2	n.428_433delCGGAGG		non_coding_transcript_exon	Exon 1 of 2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000162 AC: 4 AN: 246214 AF XY: 0.0000149

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: 0.0000364

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000548 AC: 80 AN: 1460300 Hom.: 0 AF XY: 0.0000454 AC XY: 33 AN XY: 726452

African (AFR) AF: 0.0000299 AC: 1 AN: 33472

American (AMR) AF: 0.00 AC: 0 AN: 44702

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26126

East Asian (EAS) AF: 0.00 AC: 0 AN: 39692

South Asian (SAS) AF: 0.00 AC: 0 AN: 86252

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52076

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5736

European-Non Finnish (NFE) AF: 0.0000693 AC: 77 AN: 1111900

Other (OTH) AF: 0.0000331 AC: 2 AN: 60344

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	1	-	Familial thoracic aortic aneurysm and aortic dissection (1)
-	1	-	Shprintzen-Goldberg syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		9.0

Splicing

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

Other links and lift over

dbSNP: rs762410895; hg19: chr1-2235505;