Genetic Variant ATN1:p.Gln501_Gln502del (chr12-6936728-ACAGCAG-A) – ACMG Classification: Benign (-9 pts)

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP6BA1

The NM_001940.4(ATN1):c.1503_1508delGCAGCA(p.Gln501_Gln502del) variant causes a disruptive inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0177 in 1,581,786 control chromosomes in the GnomAD database, including 919 homozygotes. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.056 ( 632 hom., cov: 0)

Exomes 𝑓: 0.014 ( 287 hom. )

Consequence

ATN1
NM_001940.4 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 1.14

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 -9 ACMG points.

BP6

Variant 12-6936728-ACAGCAG-A is Benign according to our data. Variant chr12-6936728-ACAGCAG-A is described in ClinVar as [Benign]. Clinvar id is 3055682.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr12-6936728-ACAGCAG-A is described in Lovd as [Benign]. Variant chr12-6936728-ACAGCAG-A is described in Lovd as [Likely_benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.17 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATN1	NM_001940.4 link	c.1503_1508delGCAGCA	p.Gln501_Gln502del	disruptive_inframe_deletion	Exon 5 of 10	ENST00000396684.3	NP_001931.2	P54259

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATN1	ENST00000396684.3 link	c.1503_1508delGCAGCA	p.Gln501_Gln502del	disruptive_inframe_deletion	Exon 5 of 10	1	NM_001940.4	ENSP00000379915.2		P54259
ATN1	ENST00000356654.8 link	c.1503_1508delGCAGCA	p.Gln501_Gln502del	disruptive_inframe_deletion	Exon 5 of 10	1		ENSP00000349076.3		P54259

Frequencies

GnomAD3 genomes

AF:

0.0555

AC:

8042

AN:

144894

Hom.:

630

Cov.:

show subpopulations

Gnomad AFR

AF:

0.174

Gnomad AMI

AF:

0.00113

Gnomad AMR

AF:

0.0322

Gnomad ASJ

AF:

0.00741

Gnomad EAS

AF:

0.00359

Gnomad SAS

AF:

0.0111

Gnomad FIN

AF:

0.00625

Gnomad MID

AF:

0.0419

Gnomad NFE

AF:

0.00926

Gnomad OTH

AF:

0.0596

GnomAD4 exome

AF:

0.0139

AC:

19913

AN:

1436792

Hom.:

287

AF XY:

0.0133

AC XY:

9538

AN XY:

715488

show subpopulations

Gnomad4 AFR exome

AF:

0.176

Gnomad4 AMR exome

AF:

0.0198

Gnomad4 ASJ exome

AF:

0.00986

Gnomad4 EAS exome

AF:

0.00482

Gnomad4 SAS exome

AF:

0.0103

Gnomad4 FIN exome

AF:

0.00756

Gnomad4 NFE exome

AF:

0.00936

Gnomad4 OTH exome

AF:

0.0215

GnomAD4 genome

AF:

0.0556

AC:

8063

AN:

144994

Hom.:

632

Cov.:

AF XY:

0.0541

AC XY:

3809

AN XY:

70402

show subpopulations

Gnomad4 AFR

AF:

0.174

Gnomad4 AMR

AF:

0.0321

Gnomad4 ASJ

AF:

0.00741

Gnomad4 EAS

AF:

0.00360

Gnomad4 SAS

AF:

0.0111

Gnomad4 FIN

AF:

0.00625

Gnomad4 NFE

AF:

0.00928

Gnomad4 OTH

AF:

0.0585

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

ATN1-related disorder

Benign:1

Oct 31, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as 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.

12-6936728-ACAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAG-ACAGCAGCAGCAGCAGCAGCAGCAGCAGCAG

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