chr22-45795354-GATTCT-G

Variant names:

• chr22-45795354-GATTCT-G
• rs60726084
• NM_013236.4:c.1174-11539_1174-11535delATTCT

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_013236.4(ATXN10):​c.1174-11539_1174-11535delATTCT variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: 𝑓 0.25 (3981 hom., cov: 0)
• Consequence: ATXN10 NM_013236.4 intron
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• 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.

• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.279 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATXN10	NM_013236.4	c.1174-11539_1174-11535delATTCT		intron_variant	Intron 9 of 11	ENST00000252934.10	NP_037368.1
ATXN10	NM_001167621.2	c.982-11539_982-11535delATTCT		intron_variant	Intron 8 of 10		NP_001161093.1
ATXN10	XM_047441314.1	c.1174-11539_1174-11535delATTCT		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_1174-11600delATTCT		intron_variant	Intron 9 of 11	1	NM_013236.4	ENSP00000252934.4

Frequencies

GnomAD3 genomes AF: 0.255 AC: 32187 AN: 126302 Hom.: 3977 Cov.: 0

Gnomad AFR AF: 0.284

Gnomad AMI AF: 0.214

Gnomad AMR AF: 0.240

Gnomad ASJ AF: 0.260

Gnomad EAS AF: 0.170

Gnomad SAS AF: 0.264

Gnomad FIN AF: 0.181

Gnomad MID AF: 0.228

Gnomad NFE AF: 0.258

Gnomad OTH AF: 0.236

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

GnomAD4 genome AF: 0.255 AC: 32219 AN: 126408 Hom.: 3981 Cov.: 0 AF XY: 0.248 AC XY: 15067 AN XY: 60706

African (AFR) AF: 0.284 AC: 9429 AN: 33254

American (AMR) AF: 0.240 AC: 2959 AN: 12322

Ashkenazi Jewish (ASJ) AF: 0.260 AC: 797 AN: 3070

East Asian (EAS) AF: 0.171 AC: 687 AN: 4020

South Asian (SAS) AF: 0.265 AC: 961 AN: 3620

European-Finnish (FIN) AF: 0.181 AC: 1436 AN: 7918

Middle Eastern (MID) AF: 0.217 AC: 59 AN: 272

European-Non Finnish (NFE) AF: 0.258 AC: 15317 AN: 59406

Other (OTH) AF: 0.233 AC: 399 AN: 1710

Alfa AF: 0.120 Hom.: 99

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Spinocerebellar ataxia type 10 Uncertain:1

Apr 01, 2023

Department of Pathology and Laboratory Medicine, Sinai Health System

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: research

- -

Computational scores

Source: dbNSFP v4.3

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

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;