rs782242788

chrX-135546391-AT-AchrX-135546391-AT-ATT

Variant summary

Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PVS1 PM2

The NM_001351601.3(INTS6L):c.359del(p.Leu120Ter) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000494 in 1,033,286 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. Variant has been reported in ClinVar as Uncertain significance (no stars). Variant results in nonsense mediated mRNA decay.

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 0.000049 (0 hom. 0 hem.)
• Consequence: INTS6L NM_001351601.3 frameshift
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 7.67

Genes affected

INTS6L (HGNC:27334): (integrator complex subunit 6 like) Predicted to be involved in snRNA 3'-end processing. Predicted to be part of integrator complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Pathogenic. Variant got 10 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
INTS6L	NM_001351601.3	c.359del	p.Leu120Ter	frameshift_variant	4/18	ENST00000639893.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
INTS6L	ENST00000639893.2	c.359del	p.Leu120Ter	frameshift_variant	4/18	5	NM_001351601.3	P1
INTS6L	ENST00000370752.4	c.359del	p.Leu120Ter	frameshift_variant	4/17	1
INTS6L	ENST00000493637.6	n.359del		non_coding_transcript_exon_variant	4/16	1
INTS6L	ENST00000481908.5	n.693del		non_coding_transcript_exon_variant	4/16	2

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome AF: 0.0000494 AC: 51 AN: 1033286 Hom.: 0 Cov.: 24 AF XY: 0.00 AC XY: 0 AN XY: 325292

Gnomad4 AFR exome AF: 0.000347

Gnomad4 AMR exome AF: 0.000343

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000353

Gnomad4 SAS exome AF: 0.0000456

Gnomad4 FIN exome AF: 0.0000255

Gnomad4 NFE exome AF: 0.0000357

Gnomad4 OTH exome AF: 0.0000464

GnomAD4 genome Cov.: 23

Alfa AF: 0.00135 Hom.: 1

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

Submissions by phenotype

Oromandibular-limb hypogenesis spectrum Uncertain:1

Uncertain significance, no assertion criteria provided

research

CHU Sainte-Justine Research Center, University of Montreal

Aug 12, 2016

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Computational scores

Source: dbNSFP v4.3

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: rs782242788; hg19: chrX-134680316;