1-2289210-C-T

Variant names:

• chr1-2289210-C-T
• rs2017143
• NM_003036.4:c.970-13768C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003036.4(SKI):​c.970-13768C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.54 in 152,042 control chromosomes in the GnomAD database, including 23,640 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.54 (23640 hom., cov: 31)
• Consequence: SKI NM_003036.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.25
• Publications: 6 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.753 is higher than 0.05.

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.970-13768C>T		intron	N/A	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.970-13768C>T		intron	N/A	ENSP00000367797.4	P12755
	SKI	ENST00000851187.1		c.970-13768C>T		intron	N/A	ENSP00000521247.1
	SKI	ENST00000478223.2	TSL:3	n.77-13768C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.540 AC: 81981 AN: 151924 Hom.: 23593 Cov.: 31

Gnomad AFR AF: 0.760

Gnomad AMI AF: 0.429

Gnomad AMR AF: 0.523

Gnomad ASJ AF: 0.421

Gnomad EAS AF: 0.391

Gnomad SAS AF: 0.489

Gnomad FIN AF: 0.465

Gnomad MID AF: 0.472

Gnomad NFE AF: 0.445

Gnomad OTH AF: 0.498

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

GnomAD4 genome AF: 0.540 AC: 82082 AN: 152042 Hom.: 23640 Cov.: 31 AF XY: 0.540 AC XY: 40159 AN XY: 74328

African (AFR) AF: 0.760 AC: 31543 AN: 41494

American (AMR) AF: 0.524 AC: 8007 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.421 AC: 1461 AN: 3472

East Asian (EAS) AF: 0.391 AC: 2007 AN: 5136

South Asian (SAS) AF: 0.488 AC: 2344 AN: 4808

European-Finnish (FIN) AF: 0.465 AC: 4919 AN: 10582

Middle Eastern (MID) AF: 0.486 AC: 143 AN: 294

European-Non Finnish (NFE) AF: 0.445 AC: 30224 AN: 67958

Other (OTH) AF: 0.494 AC: 1043 AN: 2110

Alfa AF: 0.466 Hom.: 62356

Bravo AF: 0.555

Asia WGS AF: 0.442 AC: 1536 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.80
DANN	Benign	0.29
PhyloP100		-1.3
Mutation Taster		=100/0	polymorphism (auto)

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: rs2017143; hg19: chr1-2220649;