Genetic Variant INTS6L:p.Leu120fs (chrX-135546391-AT-A) – ACMG Classification: Uncertain_significance (0 pts)

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

Scores

Not classified

Clinical Significance

Uncertain significance no assertion criteria provided U:1

Conservation

PhyloP100: 7.67

Publications

5 publications found

Variant links:

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]

INTS6L links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
INTS6L	NM_001351601.3 link	c.359delT	p.Leu120fs	frameshift_variant	Exon 4 of 18	ENST00000639893.2	NP_001338530.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
INTS6L	ENST00000639893.2 link	c.359delT	p.Leu120fs	frameshift_variant	Exon 4 of 18	5	NM_001351601.3	ENSP00000491427.1	A0A1W2PPI5
INTS6L	ENST00000370752.4 link	c.359delT	p.Leu120fs	frameshift_variant	Exon 4 of 17	1		ENSP00000359788.4	Q5JSJ4-1
INTS6L	ENST00000493637.6 link	n.359delT		non_coding_transcript_exon_variant	Exon 4 of 16	1
INTS6L	ENST00000481908.5 link	n.693delT		non_coding_transcript_exon_variant	Exon 4 of 16	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.000234

AC:

AN:

132442

AF XY:

0.00

show subpopulations

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:

AN:

1033286

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

325292

show subpopulations

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

African (AFR)

AF:

0.000347

AC:

AN:

23023

American (AMR)

AF:

0.000343

AC:

AN:

23348

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

17347

East Asian (EAS)

AF:

0.0000353

AC:

AN:

28332

South Asian (SAS)

AF:

0.0000456

AC:

AN:

43904

European-Finnish (FIN)

AF:

0.0000255

AC:

AN:

39147

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3747

European-Non Finnish (NFE)

AF:

0.0000357

AC:

AN:

811301

Other (OTH)

AF:

0.0000464

AC:

AN:

43137

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.248

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.00135

Hom.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Oromandibular-limb hypogenesis spectrum

Uncertain:1

Aug 12, 2016

CHU Sainte-Justine Research Center, University of Montreal

Significance:Uncertain significance

Review Status:no assertion criteria provided

Collection Method:research

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

7.7

Mutation Taster

=8/192

disease causing (fs/PTC)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over