1-2228895-G-T

Variant names:

• chr1-2228895-G-T
• rs1313492083
• NM_003036.4:c.129G>T

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The ENST00000378536.5(SKI):​c.129G>T​(p.Ala43Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000786 in 1,272,218 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. A43A) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.9e-7 (0 hom.)
• Consequence: SKI ENST00000378536.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0860
• 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, PanelApp Australia, G2P, Genomics England PanelApp, ClinGen, Orphanet, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.7).
• BP7: Synonymous conserved (PhyloP=-0.086 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000378536.5. 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.129G>T	p.Ala43Ala	synonymous	Exon 1 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.129G>T	p.Ala43Ala	synonymous	Exon 1 of 7	ENSP00000367797.4
	SKI	ENST00000704337.1		n.137+1371G>T		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.86e-7 AC: 1 AN: 1272218 Hom.: 0 Cov.: 31 AF XY: 0.00000159 AC XY: 1 AN XY: 628666

African (AFR) AF: 0.00 AC: 0 AN: 26044

American (AMR) AF: 0.00 AC: 0 AN: 25672

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20774

East Asian (EAS) AF: 0.00 AC: 0 AN: 25818

South Asian (SAS) AF: 0.00 AC: 0 AN: 71144

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 31804

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3802

European-Non Finnish (NFE) AF: 9.84e-7 AC: 1 AN: 1016496

Other (OTH) AF: 0.00 AC: 0 AN: 50664

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	12
DANN	Benign	0.77
PhyloP100		-0.086
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=99/1	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: rs1313492083; hg19: chr1-2160334;