NM_013236.4:c.1174-12802A>C

Variant names:

• chr22-45794157-A-C
• rs5764850
• NM_013236.4:c.1174-12802A>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.1174-12802A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.579 in 151,966 control chromosomes in the GnomAD database, including 26,675 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 0.58 (26675 hom., cov: 31)
• Consequence: ATXN10 NM_013236.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.502
• Publications: 9 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=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.732 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATXN10	NM_013236.4	c.1174-12802A>C		intron_variant	Intron 9 of 11	ENST00000252934.10	NP_037368.1
ATXN10	NM_001167621.2	c.982-12802A>C		intron_variant	Intron 8 of 10		NP_001161093.1
ATXN10	XM_047441314.1	c.1174-12802A>C		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.1174-12802A>C		intron_variant	Intron 9 of 11	1	NM_013236.4	ENSP00000252934.4

Frequencies

GnomAD3 genomes AF: 0.580 AC: 88035 AN: 151848 Hom.: 26669 Cov.: 31

Gnomad AFR AF: 0.387

Gnomad AMI AF: 0.630

Gnomad AMR AF: 0.698

Gnomad ASJ AF: 0.615

Gnomad EAS AF: 0.752

Gnomad SAS AF: 0.723

Gnomad FIN AF: 0.650

Gnomad MID AF: 0.661

Gnomad NFE AF: 0.632

Gnomad OTH AF: 0.620

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

GnomAD4 genome AF: 0.579 AC: 88058 AN: 151966 Hom.: 26675 Cov.: 31 AF XY: 0.584 AC XY: 43382 AN XY: 74282

African (AFR) AF: 0.387 AC: 16022 AN: 41422

American (AMR) AF: 0.698 AC: 10663 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.615 AC: 2135 AN: 3470

East Asian (EAS) AF: 0.752 AC: 3876 AN: 5156

South Asian (SAS) AF: 0.723 AC: 3479 AN: 4812

European-Finnish (FIN) AF: 0.650 AC: 6863 AN: 10554

Middle Eastern (MID) AF: 0.650 AC: 191 AN: 294

European-Non Finnish (NFE) AF: 0.632 AC: 42938 AN: 67956

Other (OTH) AF: 0.624 AC: 1316 AN: 2110

Alfa AF: 0.462 Hom.: 1288

Bravo AF: 0.576

Asia WGS AF: 0.725 AC: 2521 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	2.0
DANN	Benign	0.67
PhyloP100		-0.50
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: rs5764850; hg19: chr22-46190037;