22-45795354-GATTCTATTCTATTCTATTCTATTCTATTCTATTCTATTCTATTCT-GATTCTATTCTATTCTATTCTATTCTATTCT

Variant names:

• chr22-45795354-GATTCTATTCTATTCT-G
• rs60726084
• NM_013236.4:c.1174-11549_1174-11535delATTCTATTCTATTCT

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BS1 BS2

The NM_013236.4(ATXN10):​c.1174-11549_1174-11535delATTCTATTCTATTCT 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 0.022 (45 hom., cov: 0)
• Consequence: ATXN10 NM_013236.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.237
• Publications: 1 publications found

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)

ACMG classification

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

• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0217 (2747/126616) while in subpopulation AFR AF = 0.0357 (1188/33322). AF 95% confidence interval is 0.034. There are 45 homozygotes in GnomAd4. There are 1306 alleles in the male GnomAd4 subpopulation. Median coverage is 0. This position passed quality control check.
• BS2: High AC in GnomAd4 at 2747 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATXN10	NM_013236.4	c.1174-11549_1174-11535delATTCTATTCTATTCT		intron_variant	Intron 9 of 11	ENST00000252934.10	NP_037368.1
ATXN10	NM_001167621.2	c.982-11549_982-11535delATTCTATTCTATTCT		intron_variant	Intron 8 of 10		NP_001161093.1
ATXN10	XM_047441314.1	c.1174-11549_1174-11535delATTCTATTCTATTCT		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	c.1174-11604_1174-11590delATTCTATTCTATTCT		intron_variant	Intron 9 of 11	1	NM_013236.4	ENSP00000252934.4

Frequencies

GnomAD3 genomes AF: 0.0217 AC: 2739 AN: 126510 Hom.: 45 Cov.: 0

Gnomad AFR AF: 0.0356

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0163

Gnomad ASJ AF: 0.00715

Gnomad EAS AF: 0.00693

Gnomad SAS AF: 0.0163

Gnomad FIN AF: 0.0155

Gnomad MID AF: 0.00345

Gnomad NFE AF: 0.0185

Gnomad OTH AF: 0.0135

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

GnomAD4 genome AF: 0.0217 AC: 2747 AN: 126616 Hom.: 45 Cov.: 0 AF XY: 0.0215 AC XY: 1306 AN XY: 60830

African (AFR) AF: 0.0357 AC: 1188 AN: 33322

American (AMR) AF: 0.0163 AC: 201 AN: 12346

Ashkenazi Jewish (ASJ) AF: 0.00715 AC: 22 AN: 3076

East Asian (EAS) AF: 0.00694 AC: 28 AN: 4032

South Asian (SAS) AF: 0.0165 AC: 60 AN: 3630

European-Finnish (FIN) AF: 0.0155 AC: 123 AN: 7932

Middle Eastern (MID) AF: 0.00368 AC: 1 AN: 272

European-Non Finnish (NFE) AF: 0.0185 AC: 1100 AN: 59476

Other (OTH) AF: 0.0140 AC: 24 AN: 1714

Alfa AF: 0.0108 Hom.: 99

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.24
Mutation Taster		=100/0	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs60726084; hg19: chr22-46191234;