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

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_001940.4(ATN1):c.1479_1508dup(p.Gln493_Gln502dup) variant causes a inframe insertion change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. Q487Q) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.00045 ( 0 hom., cov: 0)

Exomes 𝑓: 0.00016 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

ATN1
NM_001940.4 inframe_insertion

Scores

Not classified

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2

High AC in GnomAd4 at 65 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ATN1	NM_001940.4 linkuse as main transcript	c.1479_1508dup	p.Gln493_Gln502dup	inframe_insertion	5/10	ENST00000396684.3
ATN1	NM_001007026.2 linkuse as main transcript	c.1479_1508dup	p.Gln493_Gln502dup	inframe_insertion	5/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ATN1	ENST00000396684.3 linkuse as main transcript	c.1479_1508dup	p.Gln493_Gln502dup	inframe_insertion	5/10	1	NM_001940.4	P1
ATN1	ENST00000356654.8 linkuse as main transcript	c.1479_1508dup	p.Gln493_Gln502dup	inframe_insertion	5/10	1		P1

Frequencies

GnomAD3 genomes

AF:

0.000448

AC:

AN:

145034

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000207

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000144

Gnomad ASJ

AF:

0.000889

Gnomad EAS

AF:

0.000634

Gnomad SAS

AF:

0.000451

Gnomad FIN

AF:

0.000298

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000645

Gnomad OTH

AF:

0.000509

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000156

AC:

225

AN:

1438900

Hom.:

Cov.:

AF XY:

0.000167

AC XY:

120

AN XY:

716718

show subpopulations

Gnomad4 AFR exome

AF:

0.0000310

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.000350

Gnomad4 EAS exome

AF:

0.00119

Gnomad4 SAS exome

AF:

0.000304

Gnomad4 FIN exome

AF:

0.000152

Gnomad4 NFE exome

AF:

0.000109

Gnomad4 OTH exome

AF:

0.000252

GnomAD4 genome

AF:

0.000448

AC:

AN:

145134

Hom.:

Cov.:

AF XY:

0.000426

AC XY:

AN XY:

70474

show subpopulations

Gnomad4 AFR

AF:

0.000206

Gnomad4 AMR

AF:

0.000144

Gnomad4 ASJ

AF:

0.000889

Gnomad4 EAS

AF:

0.000635

Gnomad4 SAS

AF:

0.000451

Gnomad4 FIN

AF:

0.000298

Gnomad4 NFE

AF:

0.000645

Gnomad4 OTH

AF:

0.000504

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 10, 2022

The c.1479_1508dupGCAGCAGCAGCAGCAGCAGCAGCAGCAGCA (p.Q493_Q502dup) alteration is located in exon 5 (coding exon 4) of the ATN1 gene. The alteration consists of an in-frame duplication of 30 nucleotides from position 1479 to 1508, resulting in the duplication of 10 residues. Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

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