ENST00000378536:c.-11C>T

Variant names:

• chr1-2228756-C-T
• rs1246353625
• NM_003036.4:c.-11C>T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The ENST00000378536.5(SKI):​c.-11C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000843 in 1,186,808 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.

• Frequency:
  • Genomes: 𝑓 0.0000068 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0000087 (0 hom.)
• Consequence: SKI ENST00000378536.5 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.526
• 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: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BS2: High AC in GnomAdExome4 at 9 AD gene.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SKI	NM_003036.4	MANE Select	c.-11C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 7	NP_003027.1	P12755
	SKI	NM_003036.4	MANE Select	c.-11C>T		5_prime_UTR	Exon 1 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.-11C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 7	ENSP00000367797.4	P12755
	SKI	ENST00000378536.5	TSL:1 MANE Select	c.-11C>T		5_prime_UTR	Exon 1 of 7	ENSP00000367797.4	P12755
	SKI	ENST00000851187.1		c.-11C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 7	ENSP00000521247.1

Frequencies

GnomAD3 genomes AF: 0.00000682 AC: 1 AN: 146644 Hom.: 0 Cov.: 31

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: 0.0000152

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000865 AC: 9 AN: 1040164 Hom.: 0 Cov.: 30 AF XY: 0.00000795 AC XY: 4 AN XY: 502994

African (AFR) AF: 0.00 AC: 0 AN: 20372

American (AMR) AF: 0.00 AC: 0 AN: 12866

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14116

East Asian (EAS) AF: 0.00 AC: 0 AN: 15174

South Asian (SAS) AF: 0.00 AC: 0 AN: 37332

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 16136

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2632

European-Non Finnish (NFE) AF: 0.0000102 AC: 9 AN: 883488

Other (OTH) AF: 0.00 AC: 0 AN: 38048

GnomAD4 genome AF: 0.00000682 AC: 1 AN: 146644 Hom.: 0 Cov.: 31 AF XY: 0.0000140 AC XY: 1 AN XY: 71346

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 40664

American (AMR) AF: 0.00 AC: 0 AN: 14832

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3398

East Asian (EAS) AF: 0.00 AC: 0 AN: 5032

South Asian (SAS) AF: 0.00 AC: 0 AN: 4786

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8774

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 308

European-Non Finnish (NFE) AF: 0.0000152 AC: 1 AN: 65942

Other (OTH) AF: 0.00 AC: 0 AN: 2000

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	18
DANN	Benign	0.94
PhyloP100		-0.53
PromoterAI		-0.035	Neutral
RBP_binding_hub_radar		1.1
RBP_regulation_power_radar		2.9

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: rs1246353625; hg19: chr1-2160195;