Variant chr12-6936728-A-ACAGCAGCAGCAG 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.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

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 = 0.058 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.1497_1508dup	p.Gln499_Gln502dup	inframe_insertion	5/10	ENST00000396684.3
ATN1	NM_001007026.2 linkuse as main transcript	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 linkuse as main transcript	c.1497_1508dup	p.Gln499_Gln502dup	inframe_insertion	5/10	1	NM_001940.4	P1
ATN1	ENST00000356654.8 linkuse as main transcript	c.1497_1508dup	p.Gln499_Gln502dup	inframe_insertion	5/10	1		P1

Frequencies

GnomAD3 genomes

AF:

0.0120

AC:

1742

AN:

145014

Hom.:

Cov.:

show subpopulations

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.:

Cov.:

AF XY:

0.0131

AC XY:

9354

AN XY:

716222

show subpopulations

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.:

Cov.:

AF XY:

0.0121

AC XY:

855

AN XY:

70464

show subpopulations

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

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