Variant chr12-6936728-A-ACAGCAGCAG details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001940.4(ATN1):c.1500_1508dup(p.Gln500_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 0.020 ( 77 hom., cov: 0)

Exomes 𝑓: 0.019 ( 83 hom. )

Failed GnomAD Quality Control

Consequence

ATN1
NM_001940.4 inframe_insertion

Scores

Not classified

Clinical Significance

Not reported in ClinVar

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.114 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ATN1	NM_001940.4 linkuse as main transcript	c.1500_1508dup	p.Gln500_Gln502dup	inframe_insertion	5/10	ENST00000396684.3
ATN1	NM_001007026.2 linkuse as main transcript	c.1500_1508dup	p.Gln500_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.1500_1508dup	p.Gln500_Gln502dup	inframe_insertion	5/10	1	NM_001940.4	P1
ATN1	ENST00000356654.8 linkuse as main transcript	c.1500_1508dup	p.Gln500_Gln502dup	inframe_insertion	5/10	1		P1

Frequencies

GnomAD3 genomes

AF:

0.0205

AC:

2966

AN:

145006

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0145

Gnomad AMI

AF:

0.00113

Gnomad AMR

AF:

0.0160

Gnomad ASJ

AF:

0.0468

Gnomad EAS

AF:

0.122

Gnomad SAS

AF:

0.0478

Gnomad FIN

AF:

0.0236

Gnomad MID

AF:

0.0129

Gnomad NFE

AF:

0.0139

Gnomad OTH

AF:

0.0316

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0185

AC:

26637

AN:

1437720

Hom.:

Cov.:

AF XY:

0.0193

AC XY:

13793

AN XY:

716096

show subpopulations

Gnomad4 AFR exome

AF:

0.0142

Gnomad4 AMR exome

AF:

0.0108

Gnomad4 ASJ exome

AF:

0.0393

Gnomad4 EAS exome

AF:

0.110

Gnomad4 SAS exome

AF:

0.0412

Gnomad4 FIN exome

AF:

0.0189

Gnomad4 NFE exome

AF:

0.0132

Gnomad4 OTH exome

AF:

0.0227

GnomAD4 genome

AF:

0.0204

AC:

2966

AN:

145106

Hom.:

Cov.:

AF XY:

0.0221

AC XY:

1560

AN XY:

70466

show subpopulations

Gnomad4 AFR

AF:

0.0144

Gnomad4 AMR

AF:

0.0160

Gnomad4 ASJ

AF:

0.0468

Gnomad4 EAS

AF:

0.123

Gnomad4 SAS

AF:

0.0476

Gnomad4 FIN

AF:

0.0236

Gnomad4 NFE

AF:

0.0139

Gnomad4 OTH

AF:

0.0333

ClinVar

Not reported in ClinVar

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over