rs782242788

Variant names:

• chrX-135546391-AT-A
• rs782242788
• NM_001351601.3:c.359delT

Your query was ambiguous. Multiple possible variants found:

• chrX-135546391-AT-A
• chrX-135546391-AT-ATT

Variant summary

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

The NM_001351601.3(INTS6L):​c.359delT​(p.Leu120fs) 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
• Publications: 5 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001351601.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	INTS6L	NM_001351601.3	MANE Select	c.359delT	p.Leu120fs	frameshift	Exon 4 of 18	NP_001338530.1	A0A1W2PPI5
	INTS6L	NM_182540.7		c.359delT	p.Leu120fs	frameshift	Exon 4 of 17	NP_872346.3	Q5JSJ4-1
	INTS6L	NM_001351603.3		c.359delT	p.Leu120fs	frameshift	Exon 4 of 18	NP_001338532.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	INTS6L	ENST00000639893.2	TSL:5 MANE Select	c.359delT	p.Leu120fs	frameshift	Exon 4 of 18	ENSP00000491427.1	A0A1W2PPI5
	INTS6L	ENST00000370752.4	TSL:1	c.359delT	p.Leu120fs	frameshift	Exon 4 of 17	ENSP00000359788.4	Q5JSJ4-1
	INTS6L	ENST00000493637.6	TSL:1	n.359delT		non_coding_transcript_exon	Exon 4 of 16

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD2 exomes AF: 0.000234 AC: 31 AN: 132442 AF XY: 0.00

Gnomad AFR exome AF: 0.000484

Gnomad AMR exome AF: 0.000822

Gnomad ASJ exome AF: 0.000199

Gnomad EAS exome AF: 0.000315

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000124

Gnomad OTH exome AF: 0.000356

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

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.000347 AC: 8 AN: 23023

American (AMR) AF: 0.000343 AC: 8 AN: 23348

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17347

East Asian (EAS) AF: 0.0000353 AC: 1 AN: 28332

South Asian (SAS) AF: 0.0000456 AC: 2 AN: 43904

European-Finnish (FIN) AF: 0.0000255 AC: 1 AN: 39147

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3747

European-Non Finnish (NFE) AF: 0.0000357 AC: 29 AN: 811301

Other (OTH) AF: 0.0000464 AC: 2 AN: 43137

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 23

Alfa AF: 0.00135 Hom.: 1

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	1	-	Oromandibular-limb hypogenesis spectrum (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		7.7
Mutation Taster		=8/192	disease causing (fs/PTC)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs782242788;

hg19: chrX-134680316;

COSMIC: COSV66083686;