12-6936728-A-ACAGCAGCAGCAG

Position:

• chr12-6936728-A-ACAGCAGCAGCAG

Variant summary

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

The NM_001940.4(ATN1):​c.1497_1508dup​(p.Gln499_Gln502dup) variant causes a inframe insertion change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. Q487Q) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.012 (24 hom., cov: 0)
  • Exomes 𝑓: 0.013 (81 hom.)
  • Failed GnomAD Quality Control
• Consequence: ATN1 NM_001940.4 inframe_insertion
• Clinical Significance: Not reported in ClinVar
• 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 Benign. Variant got -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.058 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ATN1	NM_001940.4	c.1497_1508dup	p.Gln499_Gln502dup	inframe_insertion	5/10	ENST00000396684.3
ATN1	NM_001007026.2	c.1497_1508dup	p.Gln499_Gln502dup	inframe_insertion	5/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ATN1	ENST00000396684.3	c.1497_1508dup	p.Gln499_Gln502dup	inframe_insertion	5/10	1	NM_001940.4	P1
ATN1	ENST00000356654.8	c.1497_1508dup	p.Gln499_Gln502dup	inframe_insertion	5/10	1		P1

Frequencies

GnomAD3 genomes AF: 0.0120 AC: 1742 AN: 145014 Hom.: 24 Cov.: 0

Gnomad AFR AF: 0.00779

Gnomad AMI AF: 0.0180

Gnomad AMR AF: 0.0107

Gnomad ASJ AF: 0.00711

Gnomad EAS AF: 0.0640

Gnomad SAS AF: 0.0253

Gnomad FIN AF: 0.00506

Gnomad MID AF: 0.00323

Gnomad NFE AF: 0.0113

Gnomad OTH AF: 0.0158

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0126 AC: 18106 AN: 1437914 Hom.: 81 Cov.: 0 AF XY: 0.0131 AC XY: 9354 AN XY: 716222

Gnomad4 AFR exome AF: 0.00599

Gnomad4 AMR exome AF: 0.00881

Gnomad4 ASJ exome AF: 0.00658

Gnomad4 EAS exome AF: 0.0629

Gnomad4 SAS exome AF: 0.0271

Gnomad4 FIN exome AF: 0.00498

Gnomad4 NFE exome AF: 0.0105

Gnomad4 OTH exome AF: 0.0128

GnomAD4 genome AF: 0.0120 AC: 1740 AN: 145114 Hom.: 24 Cov.: 0 AF XY: 0.0121 AC XY: 855 AN XY: 70464

Gnomad4 AFR AF: 0.00777

Gnomad4 AMR AF: 0.0106

Gnomad4 ASJ AF: 0.00711

Gnomad4 EAS AF: 0.0640

Gnomad4 SAS AF: 0.0251

Gnomad4 FIN AF: 0.00506

Gnomad4 NFE AF: 0.0113

Gnomad4 OTH AF: 0.0156

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;