rs2843159

Variant names:

• chr1-2304233-C-T
• rs2843159
• NM_003036.4:c.1475-60C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_003036.4(SKI):​c.1475-60C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.185 in 1,552,814 control chromosomes in the GnomAD database, including 33,893 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.27 (7559 hom., cov: 33)
  • Exomes 𝑓: 0.18 (26334 hom.)
• Consequence: SKI NM_003036.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.915
• Publications: 12 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BP6: Variant 1-2304233-C-T is Benign according to our data. Variant chr1-2304233-C-T is described in ClinVar as Benign. ClinVar VariationId is 673795.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.496 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.1475-60C>T		intron	N/A	NP_003027.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SKI	ENST00000378536.5	TSL:1 MANE Select	c.1475-60C>T		intron	N/A	ENSP00000367797.4
	SKI	ENST00000851187.1		c.1481-60C>T		intron	N/A	ENSP00000521247.1
	SKI	ENST00000507179.1	TSL:2	n.464-60C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.275 AC: 41720 AN: 151928 Hom.: 7540 Cov.: 33

Gnomad AFR AF: 0.502

Gnomad AMI AF: 0.164

Gnomad AMR AF: 0.304

Gnomad ASJ AF: 0.137

Gnomad EAS AF: 0.298

Gnomad SAS AF: 0.344

Gnomad FIN AF: 0.172

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.149

Gnomad OTH AF: 0.248

GnomAD4 exome AF: 0.175 AC: 245719 AN: 1400772 Hom.: 26334 Cov.: 36 AF XY: 0.178 AC XY: 123260 AN XY: 691230

African (AFR) AF: 0.517 AC: 16352 AN: 31628

American (AMR) AF: 0.371 AC: 13292 AN: 35780

Ashkenazi Jewish (ASJ) AF: 0.142 AC: 3563 AN: 25148

East Asian (EAS) AF: 0.275 AC: 9827 AN: 35792

South Asian (SAS) AF: 0.321 AC: 25512 AN: 79546

European-Finnish (FIN) AF: 0.168 AC: 8276 AN: 49284

Middle Eastern (MID) AF: 0.122 AC: 693 AN: 5682

European-Non Finnish (NFE) AF: 0.145 AC: 157040 AN: 1079814

Other (OTH) AF: 0.192 AC: 11164 AN: 58098

GnomAD4 genome AF: 0.275 AC: 41787 AN: 152042 Hom.: 7559 Cov.: 33 AF XY: 0.280 AC XY: 20782 AN XY: 74336

African (AFR) AF: 0.502 AC: 20784 AN: 41440

American (AMR) AF: 0.305 AC: 4660 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.137 AC: 476 AN: 3466

East Asian (EAS) AF: 0.298 AC: 1535 AN: 5158

South Asian (SAS) AF: 0.342 AC: 1649 AN: 4820

European-Finnish (FIN) AF: 0.172 AC: 1820 AN: 10606

Middle Eastern (MID) AF: 0.129 AC: 38 AN: 294

European-Non Finnish (NFE) AF: 0.149 AC: 10152 AN: 67948

Other (OTH) AF: 0.248 AC: 524 AN: 2114

Alfa AF: 0.175 Hom.: 4064

Bravo AF: 0.294

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.78
DANN	Benign	0.62
PhyloP100		-0.92
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs2843159; hg19: chr1-2235672; COSMIC: COSV66013023; COSMIC: COSV66013023;