Variant 12-6936728-ACAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAG-ACAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAG details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP6BS2

The NM_001940.4(ATN1):c.1485_1508dup(p.Gln495_Gln502dup) variant causes a inframe insertion change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Likely benign (no stars). Synonymous variant affecting the same amino acid position (i.e. Q487Q) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0016 ( 1 hom., cov: 0)

Exomes 𝑓: 0.00082 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

ATN1
NM_001940.4 inframe_insertion

Scores

Not classified

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.621

Variant links:

Genes affected

ATN1 (HGNC:3033): (atrophin 1) Dentatorubral pallidoluysian atrophy (DRPLA) is a rare neurodegenerative disorder characterized by cerebellar ataxia, myoclonic epilepsy, choreoathetosis, and dementia. The disorder is related to the expansion from 7-35 copies to 49-93 copies of a trinucleotide repeat (CAG/CAA) within this gene. The encoded protein includes a serine repeat and a region of alternating acidic and basic amino acids, as well as the variable glutamine repeat. Alternative splicing results in two transcripts variants that encode the same protein. [provided by RefSeq, Jul 2016]

ATN1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

BP6

Variant 12-6936728-A-ACAGCAGCAGCAGCAGCAGCAGCAG is Benign according to our data. Variant chr12-6936728-A-ACAGCAGCAGCAGCAGCAGCAGCAG is described in ClinVar as [Likely_benign]. Clinvar id is 3043085.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High AC in GnomAd4 at 236 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ATN1	NM_001940.4 linkuse as main transcript	c.1485_1508dup	p.Gln495_Gln502dup	inframe_insertion	5/10	ENST00000396684.3
ATN1	NM_001007026.2 linkuse as main transcript	c.1485_1508dup	p.Gln495_Gln502dup	inframe_insertion	5/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ATN1	ENST00000396684.3 linkuse as main transcript	c.1485_1508dup	p.Gln495_Gln502dup	inframe_insertion	5/10	1	NM_001940.4	P1
ATN1	ENST00000356654.8 linkuse as main transcript	c.1485_1508dup	p.Gln495_Gln502dup	inframe_insertion	5/10	1		P1

Frequencies

GnomAD3 genomes

AF:

0.00163

AC:

236

AN:

145034

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00119

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000432

Gnomad ASJ

AF:

0.000296

Gnomad EAS

AF:

0.00127

Gnomad SAS

AF:

0.00316

Gnomad FIN

AF:

0.000397

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00234

Gnomad OTH

AF:

0.00153

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000823

AC:

1184

AN:

1438904

Hom.:

Cov.:

AF XY:

0.000917

AC XY:

657

AN XY:

716722

show subpopulations

Gnomad4 AFR exome

AF:

0.000496

Gnomad4 AMR exome

AF:

0.000224

Gnomad4 ASJ exome

AF:

0.0000779

Gnomad4 EAS exome

AF:

0.00428

Gnomad4 SAS exome

AF:

0.00180

Gnomad4 FIN exome

AF:

0.000495

Gnomad4 NFE exome

AF:

0.000691

Gnomad4 OTH exome

AF:

0.000807

GnomAD4 genome

AF:

0.00163

AC:

236

AN:

145134

Hom.:

Cov.:

AF XY:

0.00143

AC XY:

101

AN XY:

70474

show subpopulations

Gnomad4 AFR

AF:

0.00119

Gnomad4 AMR

AF:

0.000432

Gnomad4 ASJ

AF:

0.000296

Gnomad4 EAS

AF:

0.00127

Gnomad4 SAS

AF:

0.00316

Gnomad4 FIN

AF:

0.000397

Gnomad4 NFE

AF:

0.00234

Gnomad4 OTH

AF:

0.00151

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

ATN1-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jun 20, 2019

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over