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. Variant got -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

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 Likely_benign. Variant got -2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SKIL	NM_005414.5	c.1098+1535C>T		intron_variant	Intron 2 of 6	ENST00000259119.9	NP_005405.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SKIL	ENST00000259119.9	c.1098+1535C>T		intron_variant	Intron 2 of 6	1	NM_005414.5	ENSP00000259119.4

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

Gnomad4 AFR AF: 0.0000245

Gnomad4 AMR AF: 0.0000668

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.0000967

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

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;