12-6936728-ACAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAG-ACAGCAGCAGCAGCAGCAG

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP6 BA1

The NM_001940.4(ATN1):c.1491_1508del(p.Gln497_Gln502del) variant causes a inframe deletion change. The variant allele was found at a frequency of 0.00693 in 1,578,214 control chromosomes in the GnomAD database, including 266 homozygotes. Variant has been reported in Lovd as Likely benign (no stars). Synonymous variant affecting the same amino acid position (i.e. Q488Q) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.024 (136 hom., cov: 0)
  • Exomes 𝑓: 0.0052 (130 hom.)
• Consequence: ATN1 NM_001940.4 inframe_deletion
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.09

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 Benign. Variant got -9 ACMG points.

• BP6: Variant 12-6936728-ACAGCAGCAGCAGCAGCAG-A is Benign according to our data. Variant chr12-6936728-ACAGCAGCAGCAGCAGCAG-A is described in Lovd as [Likely_benign].
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0761 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ATN1	NM_001940.4	c.1491_1508del	p.Gln497_Gln502del	inframe_deletion	5/10	ENST00000396684.3
ATN1	NM_001007026.2	c.1491_1508del	p.Gln497_Gln502del	inframe_deletion	5/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ATN1	ENST00000396684.3	c.1491_1508del	p.Gln497_Gln502del	inframe_deletion	5/10	1	NM_001940.4	P1
ATN1	ENST00000356654.8	c.1491_1508del	p.Gln497_Gln502del	inframe_deletion	5/10	1		P1

Frequencies

GnomAD3 genomes AF: 0.0239 AC: 3462 AN: 145000 Hom.: 135 Cov.: 0

Gnomad AFR AF: 0.0785

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0103

Gnomad ASJ AF: 0.00296

Gnomad EAS AF: 0.00613

Gnomad SAS AF: 0.0151

Gnomad FIN AF: 0.0000992

Gnomad MID AF: 0.0226

Gnomad NFE AF: 0.00192

Gnomad OTH AF: 0.0224

GnomAD4 exome AF: 0.00521 AC: 7472 AN: 1433114 Hom.: 130 AF XY: 0.00520 AC XY: 3713 AN XY: 713844

Gnomad4 AFR exome AF: 0.0851

Gnomad4 AMR exome AF: 0.00694

Gnomad4 ASJ exome AF: 0.00413

Gnomad4 EAS exome AF: 0.00456

Gnomad4 SAS exome AF: 0.0132

Gnomad4 FIN exome AF: 0.000537

Gnomad4 NFE exome AF: 0.00195

Gnomad4 OTH exome AF: 0.0101

GnomAD4 genome AF: 0.0239 AC: 3469 AN: 145100 Hom.: 136 Cov.: 0 AF XY: 0.0240 AC XY: 1689 AN XY: 70456

Gnomad4 AFR AF: 0.0785

Gnomad4 AMR AF: 0.0103

Gnomad4 ASJ AF: 0.00296

Gnomad4 EAS AF: 0.00614

Gnomad4 SAS AF: 0.0149

Gnomad4 FIN AF: 0.0000992

Gnomad4 NFE AF: 0.00192

Gnomad4 OTH AF: 0.0227

ClinVar

Not reported in ClinVar

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;