Genetic Variant ATXN10:c.1174-11569_1174-11535delATTCTATTCTATTCTATTCTATTCTATTCTATTCT (chr22-45795354-GATTCTATTCTATTCTATTCTATTCTATTCTATTCT-G) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BS1BS2

The NM_013236.4(ATXN10):c.1174-11569_1174-11535delATTCTATTCTATTCTATTCTATTCTATTCTATTCT variant causes a intron change involving the alteration of a non-conserved nucleotide. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0050 ( 8 hom., cov: 0)

Consequence

ATXN10
NM_013236.4 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.237

Publications

1 publications found

Variant links:

Genes affected

ATXN10 (HGNC:10549): (ataxin 10) This gene encodes a protein that may function in neuron survival, neuron differentiation, and neuritogenesis. These roles may be carried out via activation of the mitogen-activated protein kinase cascade. Expansion of an ATTCT repeat from 9-32 copies to 800-4500 copies in an intronic region of this locus has been associated with spinocerebellar ataxia, type 10. Alternatively spliced transcript variants have been described.[provided by RefSeq, Jul 2016]

ATXN10 Gene-Disease associations (from GenCC):

spinocerebellar ataxia type 10
Inheritance: AD Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae)

ATXN10 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00497 (629/126640) while in subpopulation AFR AF = 0.0181 (602/33332). AF 95% confidence interval is 0.0169. There are 8 homozygotes in GnomAd4. There are 297 alleles in the male GnomAd4 subpopulation. Median coverage is 0. This position passed quality control check.

BS2

High AC in GnomAd4 at 629 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
ATXN10	NM_013236.4 link	c.1174-11569_1174-11535delATTCTATTCTATTCTATTCTATTCTATTCTATTCT	intron_variant	Intron 9 of 11	ENST00000252934.10	NP_037368.1	Q9UBB4-1
ATXN10	NM_001167621.2 link	c.982-11569_982-11535delATTCTATTCTATTCTATTCTATTCTATTCTATTCT	intron_variant	Intron 8 of 10		NP_001161093.1	Q9UBB4-2
ATXN10	XM_047441314.1 link	c.1174-11569_1174-11535delATTCTATTCTATTCTATTCTATTCTATTCTATTCT	intron_variant	Intron 9 of 11		XP_047297270.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATXN10	ENST00000252934.10 link	c.1174-11604_1174-11570delATTCTATTCTATTCTATTCTATTCTATTCTATTCT		intron_variant	Intron 9 of 11	1	NM_013236.4	ENSP00000252934.4		Q9UBB4-1

Frequencies

GnomAD3 genomes

AF:

0.00497

AC:

629

AN:

126534

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0181

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00154

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000276

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000336

Gnomad OTH

AF:

0.00294

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.00497

AC:

629

AN:

126640

Hom.:

Cov.:

AF XY:

0.00488

AC XY:

297

AN XY:

60836

show subpopulations

African (AFR)

AF:

0.0181

AC:

602

AN:

33332

American (AMR)

AF:

0.00154

AC:

AN:

12350

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3076

East Asian (EAS)

AF:

0.00

AC:

AN:

4032

South Asian (SAS)

AF:

0.000275

AC:

AN:

3630

European-Finnish (FIN)

AF:

0.00

AC:

AN:

7936

Middle Eastern (MID)

AF:

0.00

AC:

AN:

272

European-Non Finnish (NFE)

AF:

0.0000336

AC:

AN:

59482

Other (OTH)

AF:

0.00292

AC:

AN:

1714

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.528

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.24

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

22-45795354-GATTCTATTCTATTCTATTCTATTCTATTCTATTCTATTCTATTCT-GATTCTATTCT

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over