GeneBe

rs60216939

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_001940.4(ATN1):​c.1473_1508delGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCA​(p.Gln491_Gln502del) variant causes a disruptive inframe deletion change. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. Q491Q) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.000021 ( 0 hom., cov: 0)
Exomes 𝑓: 0.000015 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

ATN1
NM_001940.4 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.09

Publications

8 publications found
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 Gene-Disease associations (from GenCC):
  • congenital hypotonia, epilepsy, developmental delay, and digital anomalies
    Inheritance: AD Classification: STRONG, MODERATE Submitted by: G2P, Illumina, Ambry Genetics, Labcorp Genetics (formerly Invitae)
  • dentatorubral-pallidoluysian atrophy
    Inheritance: AD Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae)

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ATN1NM_001940.4 linkc.1473_1508delGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCA p.Gln491_Gln502del disruptive_inframe_deletion Exon 5 of 10 ENST00000396684.3 NP_001931.2 P54259

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ATN1ENST00000396684.3 linkc.1473_1508delGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCA p.Gln491_Gln502del disruptive_inframe_deletion Exon 5 of 10 1 NM_001940.4 ENSP00000379915.2 P54259
ATN1ENST00000356654.8 linkc.1473_1508delGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCA p.Gln491_Gln502del disruptive_inframe_deletion Exon 5 of 10 1 ENSP00000349076.3 P54259

Frequencies

GnomAD3 genomes
AF:
0.0000207
AC:
3
AN:
145034
Hom.:
0
Cov.:
0
show subpopulations
Gnomad AFR
AF:
0.0000517
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000150
Gnomad OTH
AF:
0.00
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
AF:
0.0000153
AC:
22
AN:
1438920
Hom.:
0
AF XY:
0.0000153
AC XY:
11
AN XY:
716734
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
32226
American (AMR)
AF:
0.0000249
AC:
1
AN:
40114
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
25686
East Asian (EAS)
AF:
0.00
AC:
0
AN:
38780
South Asian (SAS)
AF:
0.0000117
AC:
1
AN:
85558
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
52578
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5722
European-Non Finnish (NFE)
AF:
0.0000173
AC:
19
AN:
1098790
Other (OTH)
AF:
0.0000168
AC:
1
AN:
59466
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.516
Heterozygous variant carriers
0
1
3
4
6
7
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
AF:
0.0000207
AC:
3
AN:
145134
Hom.:
0
Cov.:
0
AF XY:
0.0000142
AC XY:
1
AN XY:
70474
show subpopulations
African (AFR)
AF:
0.0000516
AC:
2
AN:
38764
American (AMR)
AF:
0.00
AC:
0
AN:
13900
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3376
East Asian (EAS)
AF:
0.00
AC:
0
AN:
4722
South Asian (SAS)
AF:
0.00
AC:
0
AN:
4430
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
10080
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
288
European-Non Finnish (NFE)
AF:
0.0000150
AC:
1
AN:
66702
Other (OTH)
AF:
0.00
AC:
0
AN:
1984
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.542
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.00
Hom.:
123

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
PhyloP100
4.1
Mutation Taster
=172/28
polymorphism

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

dbSNP: rs60216939; hg19: chr12-7045891; API