3-170362964-C-T

Variant names:

• chr3-170362964-C-T
• rs13101192
• NM_005414.5:c.1098+1535C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_005414.5(SKIL):​c.1098+1535C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000199 in 150,636 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 0.000020 (0 hom., cov: 26)
• Consequence: SKIL NM_005414.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.175
• Publications: 2 publications found

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

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005414.5. 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
	SKIL	NM_005414.5	MANE Select	c.1098+1535C>T		intron	N/A	NP_005405.2
	SKIL	NM_001248008.1		c.1098+1535C>T		intron	N/A	NP_001234937.1
	SKIL	NM_001145098.3		c.1038+1535C>T		intron	N/A	NP_001138570.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SKIL	ENST00000259119.9	TSL:1 MANE Select	c.1098+1535C>T		intron	N/A	ENSP00000259119.4
	SKIL	ENST00000458537.7	TSL:1	c.1098+1535C>T		intron	N/A	ENSP00000415243.3
	SKIL	ENST00000465590.2	TSL:1	c.1098+1535C>T		intron	N/A	ENSP00000516712.1

Frequencies

GnomAD3 genomes AF: 0.0000199 AC: 3 AN: 150636 Hom.: 0 Cov.: 26

Gnomad AFR AF: 0.0000245

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000668

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0000967

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

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

GnomAD4 genome AF: 0.0000199 AC: 3 AN: 150636 Hom.: 0 Cov.: 26 AF XY: 0.00 AC XY: 0 AN XY: 73412

African (AFR) AF: 0.0000245 AC: 1 AN: 40778

American (AMR) AF: 0.0000668 AC: 1 AN: 14974

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.00 AC: 0 AN: 4746

European-Finnish (FIN) AF: 0.0000967 AC: 1 AN: 10342

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67862

Other (OTH) AF: 0.00 AC: 0 AN: 2062

Alfa AF: 0.00 Hom.: 2430

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.9
DANN	Benign	0.94
PhyloP100		-0.17

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: rs13101192; hg19: chr3-170080752;