3-63912714-A-C
Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2
The NM_001377405.1(ATXN7):c.116A>C(p.Gln39Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00041 in 1,212,584 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.00029 ( 1 hom., cov: 31)
Exomes 𝑓: 0.00043 ( 0 hom. )
Consequence
ATXN7
NM_001377405.1 missense
NM_001377405.1 missense
Scores
1
12
Clinical Significance
Conservation
PhyloP100: 0.00
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -8 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.012874275).
BS2
?
High AC in GnomAd at 43 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ATXN7 | NM_001377405.1 | c.116A>C | p.Gln39Pro | missense_variant | 3/13 | ENST00000674280.1 | |
ATXN7 | NM_001177387.1 | c.116A>C | p.Gln39Pro | missense_variant | 2/13 | ||
ATXN7 | NM_000333.4 | c.116A>C | p.Gln39Pro | missense_variant | 3/13 | ||
ATXN7 | NM_001377406.1 | c.116A>C | p.Gln39Pro | missense_variant | 2/12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ATXN7 | ENST00000674280.1 | c.116A>C | p.Gln39Pro | missense_variant | 3/13 | NM_001377405.1 | P2 |
Frequencies
GnomAD3 genomes ? AF: 0.000293 AC: 43AN: 146898Hom.: 1 Cov.: 31
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GnomAD3 exomes AF: 0.000935 AC: 30AN: 32074Hom.: 0 AF XY: 0.000938 AC XY: 17AN XY: 18122
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GnomAD4 exome AF: 0.000426 AC: 454AN: 1065578Hom.: 0 Cov.: 32 AF XY: 0.000458 AC XY: 234AN XY: 510578
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GnomAD4 genome ? AF: 0.000293 AC: 43AN: 147006Hom.: 1 Cov.: 31 AF XY: 0.000377 AC XY: 27AN XY: 71544
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jun 01, 2016 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
D
LIST_S2
Benign
T;T;T;.;.
M_CAP
Benign
T
MetaRNN
Benign
T;T;T;T;T
MetaSVM
Benign
T
MutationTaster
Benign
N;N;N;N
PrimateAI
Pathogenic
D
Vest4
0.25, 0.24, 0.28
MVP
0.19
ClinPred
T
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at