3-63912871-G-C
Variant names:
Variant summary
Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2
The NM_001377405.1(ATXN7):c.273G>C(p.Leu91Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00247 in 1,613,414 control chromosomes in the GnomAD database, including 10 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.0020 ( 0 hom., cov: 31)
Exomes 𝑓: 0.0025 ( 10 hom. )
Consequence
ATXN7
NM_001377405.1 synonymous
NM_001377405.1 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.52
Genes affected
ATXN7 (HGNC:10560): (ataxin 7) The autosomal dominant cerebellar ataxias (ADCA) are a heterogeneous group of neurodegenerative disorders characterized by progressive degeneration of the cerebellum, brain stem and spinal cord. Clinically, ADCA has been divided into three groups: ADCA types I-III. ADCAI is genetically heterogeneous, with five genetic loci, designated spinocerebellar ataxia (SCA) 1, 2, 3, 4 and 6, being assigned to five different chromosomes. ADCAII, which always presents with retinal degeneration (SCA7), and ADCAIII often referred to as the 'pure' cerebellar syndrome (SCA5), are most likely homogeneous disorders. Several SCA genes have been cloned and shown to contain CAG repeats in their coding regions. ADCA is caused by the expansion of the CAG repeats, producing an elongated polyglutamine tract in the corresponding protein. The expanded repeats are variable in size and unstable, usually increasing in size when transmitted to successive generations. This locus has been mapped to chromosome 3, and it has been determined that the diseased allele associated with spinocerebellar ataxia-7 contains 37-306 CAG repeats (near the N-terminus), compared to 4-35 in the normal allele. The encoded protein is a component of the SPT3/TAF9/GCN5 acetyltransferase (STAGA) and TBP-free TAF-containing (TFTC) chromatin remodeling complexes, and it thus plays a role in transcriptional regulation. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2016]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -11 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.52).
BP6
Variant 3-63912871-G-C is Benign according to our data. Variant chr3-63912871-G-C is described in ClinVar as [Benign]. Clinvar id is 1284420.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr3-63912871-G-C is described in Lovd as [Benign]. Variant chr3-63912871-G-C is described in Lovd as [Likely_benign].
BP7
Synonymous conserved (PhyloP=1.52 with no splicing effect.
BS2
High AC in GnomAd4 at 311 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ATXN7 | NM_001377405.1 | c.273G>C | p.Leu91Leu | synonymous_variant | Exon 3 of 13 | ENST00000674280.1 | NP_001364334.1 | |
ATXN7 | NM_001177387.1 | c.273G>C | p.Leu91Leu | synonymous_variant | Exon 2 of 13 | NP_001170858.1 | ||
ATXN7 | NM_000333.4 | c.273G>C | p.Leu91Leu | synonymous_variant | Exon 3 of 13 | NP_000324.1 | ||
ATXN7 | NM_001377406.1 | c.273G>C | p.Leu91Leu | synonymous_variant | Exon 2 of 12 | NP_001364335.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00205 AC: 312AN: 151826Hom.: 0 Cov.: 31
GnomAD3 genomes
AF:
AC:
312
AN:
151826
Hom.:
Cov.:
31
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.00165 AC: 404AN: 245476Hom.: 0 AF XY: 0.00163 AC XY: 218AN XY: 134114
GnomAD3 exomes
AF:
AC:
404
AN:
245476
Hom.:
AF XY:
AC XY:
218
AN XY:
134114
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.00251 AC: 3668AN: 1461480Hom.: 10 Cov.: 33 AF XY: 0.00243 AC XY: 1768AN XY: 727074
GnomAD4 exome
AF:
AC:
3668
AN:
1461480
Hom.:
Cov.:
33
AF XY:
AC XY:
1768
AN XY:
727074
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome AF: 0.00205 AC: 311AN: 151934Hom.: 0 Cov.: 31 AF XY: 0.00183 AC XY: 136AN XY: 74258
GnomAD4 genome
AF:
AC:
311
AN:
151934
Hom.:
Cov.:
31
AF XY:
AC XY:
136
AN XY:
74258
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
ClinVar
Significance: Benign
Submissions summary: Benign:3
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:2
-
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center
Significance: Likely benign
Review Status: no assertion criteria provided
Collection Method: clinical testing
- -
Jun 01, 2022
CeGaT Center for Human Genetics Tuebingen
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing
ATXN7: BS1, BS2 -
not specified Benign:1
-
Clinical Genetics, Academic Medical Center
Significance: Benign
Review Status: no assertion criteria provided
Collection Method: clinical testing
- -
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at