Variant 12-6936728-A-ACAGCAGCAGCAGCAG details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_ModerateBS1BS2

The NM_001940.4(ATN1):c.1494_1508dup(p.Gln498_Gln502dup) variant causes a inframe insertion change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★). Synonymous variant affecting the same amino acid position (i.e. Q487Q) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0085 ( 11 hom., cov: 0)

Exomes 𝑓: 0.010 ( 107 hom. )

Failed GnomAD Quality Control

Consequence

ATN1
NM_001940.4 inframe_insertion

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP6

Variant 12-6936728-A-ACAGCAGCAGCAGCAG is Benign according to our data. Variant chr12-6936728-A-ACAGCAGCAGCAGCAG is described in ClinVar as [Benign]. Clinvar id is 2642645.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00854 (1239/145120) while in subpopulation EAS AF= 0.0195 (92/4718). AF 95% confidence interval is 0.0163. There are 11 homozygotes in gnomad4. There are 581 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.

BS2

High AC in GnomAd4 at 1239 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ATN1	NM_001940.4 linkuse as main transcript	c.1494_1508dup	p.Gln498_Gln502dup	inframe_insertion	5/10	ENST00000396684.3
ATN1	NM_001007026.2 linkuse as main transcript	c.1494_1508dup	p.Gln498_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.1494_1508dup	p.Gln498_Gln502dup	inframe_insertion	5/10	1	NM_001940.4	P1
ATN1	ENST00000356654.8 linkuse as main transcript	c.1494_1508dup	p.Gln498_Gln502dup	inframe_insertion	5/10	1		P1

Frequencies

GnomAD3 genomes

AF:

0.00854

AC:

1239

AN:

145020

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00349

Gnomad AMI

AF:

0.0315

Gnomad AMR

AF:

0.0133

Gnomad ASJ

AF:

0.0228

Gnomad EAS

AF:

0.0195

Gnomad SAS

AF:

0.0142

Gnomad FIN

AF:

0.00188

Gnomad MID

AF:

0.00645

Gnomad NFE

AF:

0.00926

Gnomad OTH

AF:

0.0102

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0105

AC:

15039

AN:

1437896

Hom.:

107

Cov.:

AF XY:

0.0106

AC XY:

7613

AN XY:

716196

show subpopulations

Gnomad4 AFR exome

AF:

0.00301

Gnomad4 AMR exome

AF:

0.0134

Gnomad4 ASJ exome

AF:

0.0210

Gnomad4 EAS exome

AF:

0.0246

Gnomad4 SAS exome

AF:

0.0147

Gnomad4 FIN exome

AF:

0.00186

Gnomad4 NFE exome

AF:

0.00991

Gnomad4 OTH exome

AF:

0.0111

GnomAD4 genome

AF:

0.00854

AC:

1239

AN:

145120

Hom.:

Cov.:

AF XY:

0.00825

AC XY:

581

AN XY:

70464

show subpopulations

Gnomad4 AFR

AF:

0.00348

Gnomad4 AMR

AF:

0.0133

Gnomad4 ASJ

AF:

0.0228

Gnomad4 EAS

AF:

0.0195

Gnomad4 SAS

AF:

0.0142

Gnomad4 FIN

AF:

0.00188

Gnomad4 NFE

AF:

0.00927

Gnomad4 OTH

AF:

0.0106

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Mar 01, 2023

ATN1: BS1, BS2 -

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over