12-6936728-ACAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAG-ACAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAG

Variant names:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_001940.4(ATN1):c.1506_1508delGCA(p.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 0.0451 in 1,548,102 control chromosomes in the GnomAD database, including 569 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.042 ( 151 hom., cov: 0)

Exomes 𝑓: 0.045 ( 418 hom. )

Consequence

ATN1
NM_001940.4 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.621

Publications

8 publications found

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 Gene-Disease associations (from GenCC):

congenital hypotonia, epilepsy, developmental delay, and digital anomalies
Inheritance: AD Classification: STRONG, MODERATE Submitted by: G2P, Illumina, Ambry Genetics, Labcorp Genetics (formerly Invitae)
dentatorubral-pallidoluysian atrophy
Inheritance: AD Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae)

ATN1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -16 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_multiple_submitters_no_conflicts, 2 stars.

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 rank	MANE	Protein	UniProt
ATN1	NM_001940.4 link	c.1506_1508delGCA	p.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.1506_1508delGCA	p.Gln502del	disruptive_inframe_deletion	Exon 5 of 10	1	NM_001940.4	ENSP00000379915.2		P54259
ATN1	ENST00000356654.8 link	c.1506_1508delGCA	p.Gln502del	disruptive_inframe_deletion	Exon 5 of 10	1		ENSP00000349076.3		P54259

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

African (AFR)

AF:

0.0357

AC:

1143

AN:

32016

American (AMR)

AF:

0.0395

AC:

1487

AN:

37630

Ashkenazi Jewish (ASJ)

AF:

0.0485

AC:

1186

AN:

24460

East Asian (EAS)

AF:

0.0106

AC:

406

AN:

38150

South Asian (SAS)

AF:

0.0847

AC:

7015

AN:

82830

European-Finnish (FIN)

AF:

0.0212

AC:

1058

AN:

49798

Middle Eastern (MID)

AF:

0.0808

AC:

455

AN:

5628

European-Non Finnish (NFE)

AF:

0.0449

AC:

48310

AN:

1075032

Other (OTH)

AF:

0.0474

AC:

2729

AN:

57514

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.452

Heterozygous variant carriers

3188

6376

9565

12753

15941

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1886

3772

5658

7544

9430

<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

AF:

0.0419

AC:

6073

AN:

145044

Hom.:

151

Cov.:

AF XY:

0.0406

AC XY:

2862

AN XY:

70440

show subpopulations

African (AFR)

AF:

0.0371

AC:

1438

AN:

38736

American (AMR)

AF:

0.0430

AC:

597

AN:

13892

Ashkenazi Jewish (ASJ)

AF:

0.0450

AC:

152

AN:

3376

East Asian (EAS)

AF:

0.0136

AC:

AN:

4720

South Asian (SAS)

AF:

0.0789

AC:

349

AN:

4426

European-Finnish (FIN)

AF:

0.0156

AC:

157

AN:

10072

Middle Eastern (MID)

AF:

0.0833

AC:

AN:

288

European-Non Finnish (NFE)

AF:

0.0455

AC:

3035

AN:

66666

Other (OTH)

AF:

0.0475

AC:

AN:

1980

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

243

486

729

972

1215

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

148

222

296

370

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0206

Hom.:

123

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Feb 16, 2025

Laboratory of Genetics, Children's Clinical University Hospital Latvia

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

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

Benign:1

Sep 07, 2021

Fulgent Genetics, Fulgent Genetics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

ATN1-related disorder

Benign:1

Feb 07, 2022

PreventionGenetics, part of Exact Sciences

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

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

PhyloP100

0.62

Mutation Taster

=83/17

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over