chr3-63912684-G-GGCA

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP3BA1

The NM_001377405.1(ATXN7):​c.116_118dupAGC​(p.Gln39dup) variant causes a disruptive inframe insertion change. The variant allele was found at a frequency of 0.0327 in 1,083,874 control chromosomes in the GnomAD database, including 941 homozygotes. Variant has been reported in ClinVar as Uncertain significance (no stars).

Frequency

Genomes: 𝑓 0.063 ( 544 hom., cov: 23)
Exomes 𝑓: 0.028 ( 397 hom. )

Consequence

ATXN7
NM_001377405.1 disruptive_inframe_insertion

Scores

Not classified

Clinical Significance

Uncertain significance no assertion criteria provided U:1

Conservation

PhyloP100: 4.10
Variant links:
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 -9 ACMG points.

BP3
Nonframeshift variant in repetitive region in NM_001377405.1
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.154 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
ATXN7NM_001377405.1 linkuse as main transcriptc.116_118dupAGC p.Gln39dup disruptive_inframe_insertion 3/13 ENST00000674280.1 NP_001364334.1
ATXN7NM_001177387.1 linkuse as main transcriptc.116_118dupAGC p.Gln39dup disruptive_inframe_insertion 2/13 NP_001170858.1 O15265-2
ATXN7NM_000333.4 linkuse as main transcriptc.116_118dupAGC p.Gln39dup disruptive_inframe_insertion 3/13 NP_000324.1 O15265-1Q9UPD8
ATXN7NM_001377406.1 linkuse as main transcriptc.116_118dupAGC p.Gln39dup disruptive_inframe_insertion 2/12 NP_001364335.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
ATXN7ENST00000674280.1 linkuse as main transcriptc.116_118dupAGC p.Gln39dup disruptive_inframe_insertion 3/13 NM_001377405.1 ENSP00000501377.1 O15265-1

Frequencies

GnomAD3 genomes
AF:
0.0625
AC:
9030
AN:
144576
Hom.:
542
Cov.:
23
show subpopulations
Gnomad AFR
AF:
0.157
Gnomad AMI
AF:
0.00442
Gnomad AMR
AF:
0.0355
Gnomad ASJ
AF:
0.0353
Gnomad EAS
AF:
0.0416
Gnomad SAS
AF:
0.0289
Gnomad FIN
AF:
0.0197
Gnomad MID
AF:
0.0230
Gnomad NFE
AF:
0.0235
Gnomad OTH
AF:
0.0428
GnomAD3 exomes
AF:
0.0267
AC:
277
AN:
10356
Hom.:
8
AF XY:
0.0281
AC XY:
156
AN XY:
5542
show subpopulations
Gnomad AFR exome
AF:
0.150
Gnomad AMR exome
AF:
0.0628
Gnomad ASJ exome
AF:
0.0640
Gnomad EAS exome
AF:
0.0294
Gnomad SAS exome
AF:
0.0535
Gnomad FIN exome
AF:
0.00875
Gnomad NFE exome
AF:
0.0308
Gnomad OTH exome
AF:
0.0400
GnomAD4 exome
AF:
0.0281
AC:
26375
AN:
939196
Hom.:
397
Cov.:
26
AF XY:
0.0276
AC XY:
12298
AN XY:
445070
show subpopulations
Gnomad4 AFR exome
AF:
0.162
Gnomad4 AMR exome
AF:
0.0379
Gnomad4 ASJ exome
AF:
0.0315
Gnomad4 EAS exome
AF:
0.0381
Gnomad4 SAS exome
AF:
0.0288
Gnomad4 FIN exome
AF:
0.0148
Gnomad4 NFE exome
AF:
0.0249
Gnomad4 OTH exome
AF:
0.0360
GnomAD4 genome
AF:
0.0626
AC:
9057
AN:
144678
Hom.:
544
Cov.:
23
AF XY:
0.0614
AC XY:
4323
AN XY:
70392
show subpopulations
Gnomad4 AFR
AF:
0.157
Gnomad4 AMR
AF:
0.0356
Gnomad4 ASJ
AF:
0.0353
Gnomad4 EAS
AF:
0.0420
Gnomad4 SAS
AF:
0.0289
Gnomad4 FIN
AF:
0.0197
Gnomad4 NFE
AF:
0.0235
Gnomad4 OTH
AF:
0.0433

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: no assertion criteria provided
LINK: link

Submissions by phenotype

Retinal dystrophy Uncertain:1
Uncertain significance, no assertion criteria providedclinical testingInstitute of Human Genetics, Univ. Regensburg, Univ. RegensburgJan 01, 2022- -

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.

Other links and lift over

dbSNP: rs193922929; hg19: chr3-63898360; API