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

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_ModerateBA1

The NM_001940.4(ATN1):c.1506_1508del(p.Gln502del) variant causes a inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0451 in 1,548,102 control chromosomes in the GnomAD database, including 569 homozygotes. Variant has been reported in ClinVar as Likely benign (★). Synonymous variant affecting the same amino acid position (i.e. Q488Q) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.042 ( 151 hom., cov: 0)

Exomes 𝑓: 0.045 ( 418 hom. )

Consequence

ATN1
NM_001940.4 inframe_deletion

Scores

Not classified

Clinical Significance

Likely benign criteria provided, single submitter B:4

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP6

Variant 12-6936728-ACAG-A is Benign according to our data. Variant chr12-6936728-ACAG-A is described in ClinVar as [Likely_benign]. Clinvar id is 1174682.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr12-6936728-ACAG-A is described in Lovd as [Benign]. Variant chr12-6936728-ACAG-A is described in Lovd as [Likely_benign]. Variant chr12-6936728-ACAG-A is described in Lovd as [Likely_benign]. Variant chr12-6936728-ACAG-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.072 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ATN1	NM_001940.4 linkuse as main transcript	c.1506_1508del	p.Gln502del	inframe_deletion	5/10	ENST00000396684.3
ATN1	NM_001007026.2 linkuse as main transcript	c.1506_1508del	p.Gln502del	inframe_deletion	5/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ATN1	ENST00000396684.3 linkuse as main transcript	c.1506_1508del	p.Gln502del	inframe_deletion	5/10	1	NM_001940.4	P1
ATN1	ENST00000356654.8 linkuse as main transcript	c.1506_1508del	p.Gln502del	inframe_deletion	5/10	1		P1

Frequencies

GnomAD3 genomes

AF:

0.0419

AC:

6069

AN:

144946

Hom.:

152

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0370

Gnomad AMI

AF:

0.184

Gnomad AMR

AF:

0.0429

Gnomad ASJ

AF:

0.0450

Gnomad EAS

AF:

0.0135

Gnomad SAS

AF:

0.0788

Gnomad FIN

AF:

0.0156

Gnomad MID

AF:

0.0871

Gnomad NFE

AF:

0.0456

Gnomad OTH

AF:

0.0480

GnomAD4 exome

AF:

0.0455

AC:

63789

AN:

1403058

Hom.:

418

AF XY:

0.0472

AC XY:

32931

AN XY:

698220

show subpopulations

Gnomad4 AFR exome

AF:

0.0357

Gnomad4 AMR exome

AF:

0.0395

Gnomad4 ASJ exome

AF:

0.0485

Gnomad4 EAS exome

AF:

0.0106

Gnomad4 SAS exome

AF:

0.0847

Gnomad4 FIN exome

AF:

0.0212

Gnomad4 NFE exome

AF:

0.0449

Gnomad4 OTH exome

AF:

0.0474

GnomAD4 genome

AF:

0.0419

AC:

6073

AN:

145044

Hom.:

151

Cov.:

AF XY:

0.0406

AC XY:

2862

AN XY:

70440

show subpopulations

Gnomad4 AFR

AF:

0.0371

Gnomad4 AMR

AF:

0.0430

Gnomad4 ASJ

AF:

0.0450

Gnomad4 EAS

AF:

0.0136

Gnomad4 SAS

AF:

0.0789

Gnomad4 FIN

AF:

0.0156

Gnomad4 NFE

AF:

0.0455

Gnomad4 OTH

AF:

0.0475

ClinVar

Significance: Likely benign

Submissions summary: Benign:4

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, no assertion criteria provided

clinical testing

Genome Diagnostics Laboratory, University Medical Center Utrecht

- -

not provided

Benign:1

Likely benign, no assertion criteria provided

clinical testing

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

- -

Dentatorubral-pallidoluysian atrophy;C5193125:Congenital hypotonia, epilepsy, developmental delay, and digital anomalies

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Fulgent Genetics, Fulgent Genetics

Sep 07, 2021

- -

ATN1-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Feb 07, 2022

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

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

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