rs773151547

Variant names:

• chr1-2306142-C-A
• rs773151547
• NM_003036.4:c.1890C>A

Your query was ambiguous. Multiple possible variants found:

• chr1-2306142-C-A
• chr1-2306142-C-T

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_Moderate BP6_Very_Strong BP7 BS2

The NM_003036.4(SKI):​c.1890C>A​(p.Ala630Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000752 in 1,595,068 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. A630A) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000062 (0 hom.)
• Consequence: SKI NM_003036.4 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.138
• Publications: 1 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, PanelApp Australia, G2P, Genomics England PanelApp, ClinGen, Orphanet, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.38).
• BP6: Variant 1-2306142-C-A is Benign according to our data. Variant chr1-2306142-C-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 1138602.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.138 with no splicing effect.
• BS2: High AC in GnomAdExome4 at 9 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SKI	NM_003036.4	MANE Select	c.1890C>A	p.Ala630Ala	synonymous	Exon 6 of 7	NP_003027.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SKI	ENST00000378536.5	TSL:1 MANE Select	c.1890C>A	p.Ala630Ala	synonymous	Exon 6 of 7	ENSP00000367797.4

Frequencies

GnomAD3 genomes AF: 0.0000197 AC: 3 AN: 152244 Hom.: 0 Cov.: 33

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: 0.0000441

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000470 AC: 1 AN: 212590 AF XY: 0.00

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: 0.0000106

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000624 AC: 9 AN: 1442824 Hom.: 0 Cov.: 32 AF XY: 0.00000279 AC XY: 2 AN XY: 715860

African (AFR) AF: 0.00 AC: 0 AN: 33284

American (AMR) AF: 0.00 AC: 0 AN: 41438

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25724

East Asian (EAS) AF: 0.00 AC: 0 AN: 38978

South Asian (SAS) AF: 0.00 AC: 0 AN: 83248

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50534

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5742

European-Non Finnish (NFE) AF: 0.00000815 AC: 9 AN: 1104166

Other (OTH) AF: 0.00 AC: 0 AN: 59710

GnomAD4 genome AF: 0.0000197 AC: 3 AN: 152244 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 74386

African (AFR) AF: 0.00 AC: 0 AN: 41464

American (AMR) AF: 0.00 AC: 0 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5196

South Asian (SAS) AF: 0.00 AC: 0 AN: 4838

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10630

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 68038

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

ClinVar

ClinVar submissions as Germline

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	Shprintzen-Goldberg syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.38
CADD	Benign	7.4
DANN	Benign	0.91
PhyloP100		-0.14
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs773151547; hg19: chr1-2237581;