rs136000

Variant names:

• chr22-45790572-G-A
• rs136000
• NM_013236.4:c.1174-16387G>A

Your query was ambiguous. Multiple possible variants found:

• chr22-45790572-G-A
• chr22-45790572-G-C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_013236.4(ATXN10):​c.1174-16387G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.861 in 152,212 control chromosomes in the GnomAD database, including 56,681 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.86 (56681 hom., cov: 32)
• Consequence: ATXN10 NM_013236.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.116
• 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.933 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATXN10	NM_013236.4	c.1174-16387G>A		intron_variant	Intron 9 of 11	ENST00000252934.10	NP_037368.1
ATXN10	NM_001167621.2	c.982-16387G>A		intron_variant	Intron 8 of 10		NP_001161093.1
ATXN10	XM_047441314.1	c.1174-16387G>A		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.1174-16387G>A		intron_variant	Intron 9 of 11	1	NM_013236.4	ENSP00000252934.4

Frequencies

GnomAD3 genomes AF: 0.861 AC: 130967 AN: 152094 Hom.: 56627 Cov.: 32

Gnomad AFR AF: 0.941

Gnomad AMI AF: 0.772

Gnomad AMR AF: 0.863

Gnomad ASJ AF: 0.852

Gnomad EAS AF: 0.789

Gnomad SAS AF: 0.834

Gnomad FIN AF: 0.841

Gnomad MID AF: 0.899

Gnomad NFE AF: 0.824

Gnomad OTH AF: 0.869

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

GnomAD4 genome AF: 0.861 AC: 131077 AN: 152212 Hom.: 56681 Cov.: 32 AF XY: 0.861 AC XY: 64072 AN XY: 74410

African (AFR) AF: 0.941 AC: 39121 AN: 41562

American (AMR) AF: 0.863 AC: 13182 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.852 AC: 2959 AN: 3472

East Asian (EAS) AF: 0.788 AC: 4071 AN: 5166

South Asian (SAS) AF: 0.834 AC: 4019 AN: 4818

European-Finnish (FIN) AF: 0.841 AC: 8916 AN: 10598

Middle Eastern (MID) AF: 0.888 AC: 261 AN: 294

European-Non Finnish (NFE) AF: 0.824 AC: 56006 AN: 68004

Other (OTH) AF: 0.870 AC: 1841 AN: 2116

Alfa AF: 0.835 Hom.: 6602

Bravo AF: 0.866

Asia WGS AF: 0.830 AC: 2890 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.2
DANN	Benign	0.30
PhyloP100		0.12
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs136000; hg19: chr22-46186452;