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

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP6BA1

The NM_001940.4(ATN1):c.1503_1508dup(p.Gln501_Gln502dup) variant causes a inframe insertion change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. Q487Q) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.049 ( 220 hom., cov: 0)

Exomes 𝑓: 0.061 ( 603 hom. )

Failed GnomAD Quality Control

Consequence

ATN1
NM_001940.4 inframe_insertion

Scores

Not classified

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:4

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 -9 ACMG points.

BP6

Variant 12-6936728-A-ACAGCAG is Benign according to our data. Variant chr12-6936728-A-ACAGCAG is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 210377.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=1, Benign=3}.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.166 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.1503_1508dup	p.Gln501_Gln502dup	inframe_insertion	5/10	ENST00000396684.3
ATN1	NM_001007026.2 linkuse as main transcript	c.1503_1508dup	p.Gln501_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.1503_1508dup	p.Gln501_Gln502dup	inframe_insertion	5/10	1	NM_001940.4	P1
ATN1	ENST00000356654.8 linkuse as main transcript	c.1503_1508dup	p.Gln501_Gln502dup	inframe_insertion	5/10	1		P1

Frequencies

GnomAD3 genomes

AF:

0.0485

AC:

7037

AN:

144952

Hom.:

219

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0228

Gnomad AMI

AF:

0.0892

Gnomad AMR

AF:

0.0464

Gnomad ASJ

AF:

0.0376

Gnomad EAS

AF:

0.176

Gnomad SAS

AF:

0.0697

Gnomad FIN

AF:

0.0205

Gnomad MID

AF:

0.0258

Gnomad NFE

AF:

0.0580

Gnomad OTH

AF:

0.0418

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0613

AC:

88020

AN:

1436500

Hom.:

603

Cov.:

AF XY:

0.0614

AC XY:

43919

AN XY:

715504

show subpopulations

Gnomad4 AFR exome

AF:

0.0200

Gnomad4 AMR exome

AF:

0.0378

Gnomad4 ASJ exome

AF:

0.0348

Gnomad4 EAS exome

AF:

0.175

Gnomad4 SAS exome

AF:

0.0697

Gnomad4 FIN exome

AF:

0.0210

Gnomad4 NFE exome

AF:

0.0613

Gnomad4 OTH exome

AF:

0.0610

GnomAD4 genome

AF:

0.0485

AC:

7036

AN:

145052

Hom.:

220

Cov.:

AF XY:

0.0473

AC XY:

3329

AN XY:

70426

show subpopulations

Gnomad4 AFR

AF:

0.0228

Gnomad4 AMR

AF:

0.0464

Gnomad4 ASJ

AF:

0.0376

Gnomad4 EAS

AF:

0.176

Gnomad4 SAS

AF:

0.0697

Gnomad4 FIN

AF:

0.0205

Gnomad4 NFE

AF:

0.0580

Gnomad4 OTH

AF:

0.0408

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:4

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not specified

Uncertain:1Benign:1

Benign, criteria provided, single submitter	clinical testing	Institute for Genomic Medicine (IGM) Clinical Laboratory, Nationwide Children's Hospital	Mar 20, 2017	Normal variation in repetative sequence -
Uncertain significance, criteria provided, single submitter	clinical testing	Genetic Services Laboratory, University of Chicago	Jun 27, 2014	- -

not provided

Benign:2

Likely benign, no assertion criteria provided	clinical testing	Department of Pathology and Laboratory Medicine, Sinai Health System	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 19, 2020	This variant is associated with the following publications: (PMID: 20977674, 15148151, 23263592, 8136840) -

Dentatorubral-pallidoluysian atrophy

Benign:1

Benign, criteria provided, single submitter

clinical testing

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Sep 28, 2015

- -

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