Variant 12-6936728-ACAGCAG-A details in Genebe, Genetics Data Aggregator

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:

Genome browser will be placed here

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/exons	MANE	Protein	UniProt
ATN1	NM_001940.4 linkuse as main transcript	c.1503_1508delGCAGCA	p.Gln501_Gln502del	disruptive_inframe_deletion	5/10	ENST00000396684.3	NP_001931.2	P54259

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ATN1	ENST00000396684.3 linkuse as main transcript	c.1503_1508delGCAGCA	p.Gln501_Gln502del	disruptive_inframe_deletion	5/10	1	NM_001940.4	ENSP00000379915.2		P54259
ATN1	ENST00000356654.8 linkuse as main transcript	c.1503_1508delGCAGCA	p.Gln501_Gln502del	disruptive_inframe_deletion	5/10	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

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 31, 2019

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.

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