12-6936728-ACAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAG-ACAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAG

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_Moderate BS2

The NM_001940.4(ATN1):c.1485_1508dup(p.Gln495_Gln502dup) variant causes a inframe insertion change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Likely benign (★). Synonymous variant affecting the same amino acid position (i.e. Q487Q) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.0016 (1 hom., cov: 0)
  • Exomes 𝑓: 0.00082 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ATN1 NM_001940.4 inframe_insertion
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.621

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]

ACMG classification

Verdict is Likely_benign. Variant got -6 ACMG points.

• BP6: Variant 12-6936728-A-ACAGCAGCAGCAGCAGCAGCAGCAG is Benign according to our data. Variant chr12-6936728-A-ACAGCAGCAGCAGCAGCAGCAGCAG is described in ClinVar as [Likely_benign]. Clinvar id is 3043085.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd at 236 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ATN1	NM_001940.4	c.1485_1508dup	p.Gln495_Gln502dup	inframe_insertion	5/10	ENST00000396684.3
ATN1	NM_001007026.2	c.1485_1508dup	p.Gln495_Gln502dup	inframe_insertion	5/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ATN1	ENST00000396684.3	c.1485_1508dup	p.Gln495_Gln502dup	inframe_insertion	5/10	1	NM_001940.4	P1
ATN1	ENST00000356654.8	c.1485_1508dup	p.Gln495_Gln502dup	inframe_insertion	5/10	1		P1

Frequencies

GnomAD3 genomes AF: 0.00163 AC: 236 AN: 145034 Hom.: 1 Cov.: 0

Gnomad AFR AF: 0.00119

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000432

Gnomad ASJ AF: 0.000296

Gnomad EAS AF: 0.00127

Gnomad SAS AF: 0.00316

Gnomad FIN AF: 0.000397

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00234

Gnomad OTH AF: 0.00153

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000823 AC: 1184 AN: 1438904 Hom.: 0 Cov.: 0 AF XY: 0.000917 AC XY: 657 AN XY: 716722

Gnomad4 AFR exome AF: 0.000496

Gnomad4 AMR exome AF: 0.000224

Gnomad4 ASJ exome AF: 0.0000779

Gnomad4 EAS exome AF: 0.00428

Gnomad4 SAS exome AF: 0.00180

Gnomad4 FIN exome AF: 0.000495

Gnomad4 NFE exome AF: 0.000691

Gnomad4 OTH exome AF: 0.000807

GnomAD4 genome AF: 0.00163 AC: 236 AN: 145134 Hom.: 1 Cov.: 0 AF XY: 0.00143 AC XY: 101 AN XY: 70474

Gnomad4 AFR AF: 0.00119

Gnomad4 AMR AF: 0.000432

Gnomad4 ASJ AF: 0.000296

Gnomad4 EAS AF: 0.00127

Gnomad4 SAS AF: 0.00316

Gnomad4 FIN AF: 0.000397

Gnomad4 NFE AF: 0.00234

Gnomad4 OTH AF: 0.00151

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

ATN1-related disorder Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Jun 20, 2019

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

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs60216939; hg19: chr12-7045891;