rs13101192

Positions:

• chr3-170362964-C-G
• chr3-170362964-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005414.5(SKIL):​c.1098+1535C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.756 in 150,642 control chromosomes in the GnomAD database, including 44,254 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 0.76 (44254 hom., cov: 26)
• Consequence: SKIL NM_005414.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.175

Genes affected

SKIL (HGNC:10897): (SKI like proto-oncogene) The protein encoded by this gene is a component of the SMAD pathway, which regulates cell growth and differentiation through transforming growth factor-beta (TGFB). In the absence of ligand, the encoded protein binds to the promoter region of TGFB-responsive genes and recruits a nuclear repressor complex. TGFB signaling causes SMAD3 to enter the nucleus and degrade this protein, allowing these genes to be activated. Four transcript variants encoding three different isoforms have been found for this gene. [provided by RefSeq, Oct 2011]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.915 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SKIL	NM_005414.5	c.1098+1535C>G		intron_variant		ENST00000259119.9	NP_005405.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SKIL	ENST00000259119.9	c.1098+1535C>G		intron_variant		1	NM_005414.5	ENSP00000259119.4

Frequencies

GnomAD3 genomes AF: 0.757 AC: 113878 AN: 150526 Hom.: 44246 Cov.: 26

Gnomad AFR AF: 0.556

Gnomad AMI AF: 0.872

Gnomad AMR AF: 0.813

Gnomad ASJ AF: 0.826

Gnomad EAS AF: 0.937

Gnomad SAS AF: 0.715

Gnomad FIN AF: 0.874

Gnomad MID AF: 0.775

Gnomad NFE AF: 0.831

Gnomad OTH AF: 0.764

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

GnomAD4 genome AF: 0.756 AC: 113917 AN: 150642 Hom.: 44254 Cov.: 26 AF XY: 0.758 AC XY: 55691 AN XY: 73474

Gnomad4 AFR AF: 0.555

Gnomad4 AMR AF: 0.813

Gnomad4 ASJ AF: 0.826

Gnomad4 EAS AF: 0.937

Gnomad4 SAS AF: 0.716

Gnomad4 FIN AF: 0.874

Gnomad4 NFE AF: 0.831

Gnomad4 OTH AF: 0.761

Alfa AF: 0.733 Hom.: 2430

Bravo AF: 0.748

Asia WGS AF: 0.768 AC: 2667 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	1.5
DANN	Benign	0.26

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

Publications

LitVar

Other links and lift over

dbSNP: rs13101192; hg19: chr3-170080752;