Variant 3-63912714-A-AGCAGCAGCAGCC details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP3BS2

The NM_001377405.1(ATXN7):c.118_119insAGCAGCAGCCGC(p.Gln39_Pro40insGlnGlnGlnPro) variant causes a disruptive inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000482 in 1,212,042 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Uncertain significance (no stars).

Frequency

Genomes: 𝑓 0.00072 ( 1 hom., cov: 31)

Exomes 𝑓: 0.00045 ( 0 hom. )

Consequence

ATXN7
NM_001377405.1 disruptive_inframe_insertion

Scores

Not classified

Clinical Significance

Uncertain significance no assertion criteria provided U:1

Conservation

PhyloP100: 0.825

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]

ATXN7 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

BP3

Nonframeshift variant in repetitive region in NM_001377405.1

BS2

High AC in GnomAd4 at 106 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATXN7	NM_001377405.1 linkuse as main transcript	c.118_119insAGCAGCAGCCGC	p.Gln39_Pro40insGlnGlnGlnPro	disruptive_inframe_insertion	3/13	ENST00000674280.1	NP_001364334.1
ATXN7	NM_001177387.1 linkuse as main transcript	c.118_119insAGCAGCAGCCGC	p.Gln39_Pro40insGlnGlnGlnPro	disruptive_inframe_insertion	2/13		NP_001170858.1	O15265-2
ATXN7	NM_000333.4 linkuse as main transcript	c.118_119insAGCAGCAGCCGC	p.Gln39_Pro40insGlnGlnGlnPro	disruptive_inframe_insertion	3/13		NP_000324.1	O15265-1Q9UPD8
ATXN7	NM_001377406.1 linkuse as main transcript	c.118_119insAGCAGCAGCCGC	p.Gln39_Pro40insGlnGlnGlnPro	disruptive_inframe_insertion	2/12		NP_001364335.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ATXN7	ENST00000674280.1 linkuse as main transcript	c.118_119insAGCAGCAGCCGC	p.Gln39_Pro40insGlnGlnGlnPro	disruptive_inframe_insertion	3/13		NM_001377405.1	ENSP00000501377.1		O15265-1

Frequencies

GnomAD3 genomes

AF:

0.000728

AC:

107

AN:

146896

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000744

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00114

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00124

Gnomad SAS

AF:

0.000629

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000738

Gnomad OTH

AF:

0.000987

GnomAD4 exome

AF:

0.000449

AC:

478

AN:

1065038

Hom.:

Cov.:

AF XY:

0.000451

AC XY:

230

AN XY:

510316

show subpopulations

Gnomad4 AFR exome

AF:

0.000239

Gnomad4 AMR exome

AF:

0.000262

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000101

Gnomad4 SAS exome

AF:

0.000424

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000480

Gnomad4 OTH exome

AF:

0.000621

GnomAD4 genome

AF:

0.000721

AC:

106

AN:

147004

Hom.:

Cov.:

AF XY:

0.000797

AC XY:

AN XY:

71546

show subpopulations

Gnomad4 AFR

AF:

0.000742

Gnomad4 AMR

AF:

0.00114

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00125

Gnomad4 SAS

AF:

0.000630

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000723

Gnomad4 OTH

AF:

0.000977

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 provided

clinical testing

Institute of Human Genetics, Univ. Regensburg, Univ. Regensburg

Jan 01, 2023

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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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over