rs193920861

Variant names:

• chr8-94824926-TG-T
• rs193920861
• NM_017864.4:c.166delG

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_017864.4(INTS8):​c.166delG​(p.Glu56AsnfsTer26) variant causes a frameshift change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (no stars). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 30)
• Consequence: INTS8 NM_017864.4 frameshift
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 3.97
• Publications: 0 publications found

Genes affected

INTS8 (HGNC:26048): (integrator complex subunit 8) This gene encodes a subunit of the Integrator complex which is involved in the cleavage of small nuclear RNAs U1 and U2 within the nucleus. The encoded protein associates with RNA polymerase II and is recruited to the U1 and U2 small nuclear RNA genes. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2012]

INTS8 Gene-Disease associations (from GenCC):

• neurodevelopmental disorder with cerebellar hypoplasia and spasticity

  Inheritance: Unknown, AR Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), PanelApp Australia

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
INTS8	NM_017864.4	c.166delG	p.Glu56AsnfsTer26	frameshift_variant	Exon 2 of 27	ENST00000523731.6	NP_060334.2
INTS8	XM_047421951.1	c.166delG	p.Glu56AsnfsTer26	frameshift_variant	Exon 2 of 23		XP_047277907.1
INTS8	NR_073444.2	n.311delG		non_coding_transcript_exon_variant	Exon 2 of 29
INTS8	NR_073445.2	n.311delG		non_coding_transcript_exon_variant	Exon 2 of 28

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
INTS8	ENST00000523731.6	c.166delG	p.Glu56AsnfsTer26	frameshift_variant	Exon 2 of 27	1	NM_017864.4	ENSP00000430338.1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 30

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

Submissions by phenotype

Prostate cancer Uncertain:1

-

Science for Life laboratory, Karolinska Institutet

Significance: Uncertain significance

Review Status: no assertion criteria provided

Collection Method: literature only

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		4.0

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.26		Details are displayed if max score is > 0.2
DS_AL_spliceai		0.26		Position offset: -33

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs193920861; hg19: chr8-95837154; COSMIC: COSV58249585; COSMIC: COSV58249585;