chr12-6935780-G-T

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP7BS2

The NM_001940.4(ATN1):​c.513G>T​(p.Pro171Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000233 in 1,461,340 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 31)
Exomes 𝑓: 0.000023 ( 0 hom. )

Consequence

ATN1
NM_001940.4 synonymous

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -4.78
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.84).
BP7
Synonymous conserved (PhyloP=-4.78 with no splicing effect.
BS2
High AC in GnomAdExome4 at 34 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ATN1NM_001940.4 linkc.513G>T p.Pro171Pro synonymous_variant 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.513G>T p.Pro171Pro synonymous_variant Exon 5 of 10 1 NM_001940.4 ENSP00000379915.2 P54259
ATN1ENST00000356654.8 linkc.513G>T p.Pro171Pro synonymous_variant Exon 5 of 10 1 ENSP00000349076.3 P54259

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD3 exomes
AF:
0.00000400
AC:
1
AN:
250136
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
135286
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000888
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000233
AC:
34
AN:
1461340
Hom.:
0
Cov.:
38
AF XY:
0.0000206
AC XY:
15
AN XY:
726972
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000297
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
Cov.:
31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.84
CADD
Benign
0.0070
DANN
Benign
0.80
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
Details are displayed if max score is > 0.2

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.

Other links and lift over

dbSNP: rs144111044; hg19: chr12-7044943; API