12-6936728-ACAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAG-ACAGCAGCAGCAGCAGCAG

Position:

• chr12-6936728-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).

• 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	Protein	UniProt
ATN1	NM_001940.4	c.1491_1508del	p.Gln497_Gln502del	inframe_deletion	5/10	ENST00000396684.3	NP_001931.2
ATN1	NM_001007026.2	c.1491_1508del	p.Gln497_Gln502del	inframe_deletion	5/10		NP_001007027.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ATN1	ENST00000396684.3	c.1491_1508del	p.Gln497_Gln502del	inframe_deletion	5/10	1	NM_001940.4	ENSP00000379915	P1
ATN1	ENST00000356654.8	c.1491_1508del	p.Gln497_Gln502del	inframe_deletion	5/10	1		ENSP00000349076	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;