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

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_001940.4(ATN1):c.1500_1508delGCAGCAGCA(p.Gln500_Gln502del) variant causes a disruptive inframe deletion change. The variant allele was found at a frequency of 0.0314 in 1,583,048 control chromosomes in the GnomAD database, including 1,748 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.081 ( 1075 hom., cov: 0)

Exomes 𝑓: 0.026 ( 673 hom. )

Consequence

ATN1
NM_001940.4 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

Uncertain significance criteria provided, single submitter U:1B:2

Conservation

PhyloP100: 4.09

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 -8 ACMG points.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.227 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATN1	NM_001940.4 link	c.1500_1508delGCAGCAGCA	p.Gln500_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.1500_1508delGCAGCAGCA	p.Gln500_Gln502del	disruptive_inframe_deletion	Exon 5 of 10	1	NM_001940.4	ENSP00000379915.2		P54259
ATN1	ENST00000356654.8 link	c.1500_1508delGCAGCAGCA	p.Gln500_Gln502del	disruptive_inframe_deletion	Exon 5 of 10	1		ENSP00000349076.3		P54259

Frequencies

GnomAD3 genomes

AF:

0.0812

AC:

11766

AN:

144852

Hom.:

1067

Cov.:

show subpopulations

Gnomad AFR

AF:

0.231

Gnomad AMI

AF:

0.00450

Gnomad AMR

AF:

0.0633

Gnomad ASJ

AF:

0.0459

Gnomad EAS

AF:

0.0351

Gnomad SAS

AF:

0.0714

Gnomad FIN

AF:

0.00853

Gnomad MID

AF:

0.0355

Gnomad NFE

AF:

0.0170

Gnomad OTH

AF:

0.0674

GnomAD4 exome

AF:

0.0263

AC:

37875

AN:

1438100

Hom.:

673

AF XY:

0.0274

AC XY:

19596

AN XY:

716348

show subpopulations

Gnomad4 AFR exome

AF:

0.224

Gnomad4 AMR exome

AF:

0.0764

Gnomad4 ASJ exome

AF:

0.0486

Gnomad4 EAS exome

AF:

0.0300

Gnomad4 SAS exome

AF:

0.0719

Gnomad4 FIN exome

AF:

0.00921

Gnomad4 NFE exome

AF:

0.0147

Gnomad4 OTH exome

AF:

0.0377

GnomAD4 genome

AF:

0.0814

AC:

11805

AN:

144948

Hom.:

1075

Cov.:

AF XY:

0.0801

AC XY:

5640

AN XY:

70386

show subpopulations

Gnomad4 AFR

AF:

0.231

Gnomad4 AMR

AF:

0.0638

Gnomad4 ASJ

AF:

0.0459

Gnomad4 EAS

AF:

0.0345

Gnomad4 SAS

AF:

0.0715

Gnomad4 FIN

AF:

0.00853

Gnomad4 NFE

AF:

0.0170

Gnomad4 OTH

AF:

0.0662

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:2

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

not specified

Uncertain:1

Mar 23, 2020

Al Jalila Children’s Genomics Center, Al Jalila Childrens Speciality Hospital

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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