Genetic Variant NM_001377405.1:c.118_119insAGCAGCAGCAGCAGCAGCAGCCGC (chr3-63912714-A-AGCAGCAGCAGCAGCAGCAGCAGCC) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP3

The NM_001377405.1(ATXN7):c.118_119insAGCAGCAGCAGCAGCAGCAGCCGC(p.Gln39_Pro40insGlnGlnGlnGlnGlnGlnGlnPro) variant causes a disruptive inframe insertion change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.000015 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

ATXN7
NM_001377405.1 disruptive_inframe_insertion

Scores

Not classified

Clinical Significance

Not reported in ClinVar

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 Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP3

Nonframeshift variant in repetitive region in NM_001377405.1

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATXN7	NM_001377405.1 link	c.118_119insAGCAGCAGCAGCAGCAGCAGCCGC	p.Gln39_Pro40insGlnGlnGlnGlnGlnGlnGlnPro	disruptive_inframe_insertion	Exon 3 of 13	ENST00000674280.1	NP_001364334.1
ATXN7	NM_001177387.1 link	c.118_119insAGCAGCAGCAGCAGCAGCAGCCGC	p.Gln39_Pro40insGlnGlnGlnGlnGlnGlnGlnPro	disruptive_inframe_insertion	Exon 2 of 13		NP_001170858.1	O15265-2
ATXN7	NM_000333.4 link	c.118_119insAGCAGCAGCAGCAGCAGCAGCCGC	p.Gln39_Pro40insGlnGlnGlnGlnGlnGlnGlnPro	disruptive_inframe_insertion	Exon 3 of 13		NP_000324.1	O15265-1Q9UPD8
ATXN7	NM_001377406.1 link	c.118_119insAGCAGCAGCAGCAGCAGCAGCCGC	p.Gln39_Pro40insGlnGlnGlnGlnGlnGlnGlnPro	disruptive_inframe_insertion	Exon 2 of 12		NP_001364335.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATXN7	ENST00000674280.1 link	c.118_119insAGCAGCAGCAGCAGCAGCAGCCGC	p.Gln39_Pro40insGlnGlnGlnGlnGlnGlnGlnPro	disruptive_inframe_insertion	Exon 3 of 13		NM_001377405.1	ENSP00000501377.1		O15265-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000150

AC:

AN:

1065642

Hom.:

Cov.:

AF XY:

0.0000157

AC XY:

AN XY:

510610

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:

0.0000178

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over