rs9614781

Variant names:

• chr22-45797062-C-G
• rs9614781
• NM_013236.4:c.1174-9897C>G

Variant summary

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

The NM_013236.4(ATXN10):​c.1174-9897C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.047 in 152,202 control chromosomes in the GnomAD database, including 203 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 0.047 (203 hom., cov: 33)
• Consequence: ATXN10 NM_013236.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.448
• Publications: 3 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=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0588 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_013236.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATXN10	NM_013236.4	MANE Select	c.1174-9897C>G		intron	N/A	NP_037368.1
	ATXN10	NM_001167621.2		c.982-9897C>G		intron	N/A	NP_001161093.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATXN10	ENST00000252934.10	TSL:1 MANE Select	c.1174-9897C>G		intron	N/A	ENSP00000252934.4
	ATXN10	ENST00000381061.8	TSL:2	c.982-9897C>G		intron	N/A	ENSP00000370449.4
	ATXN10	ENST00000435026.5	TSL:3	c.430-9897C>G		intron	N/A	ENSP00000391117.1

Frequencies

GnomAD3 genomes AF: 0.0470 AC: 7144 AN: 152084 Hom.: 202 Cov.: 33

Gnomad AFR AF: 0.0255

Gnomad AMI AF: 0.0363

Gnomad AMR AF: 0.0394

Gnomad ASJ AF: 0.0737

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.0213

Gnomad FIN AF: 0.0833

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.0603

Gnomad OTH AF: 0.0455

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

GnomAD4 genome AF: 0.0470 AC: 7152 AN: 152202 Hom.: 203 Cov.: 33 AF XY: 0.0480 AC XY: 3571 AN XY: 74440

African (AFR) AF: 0.0255 AC: 1060 AN: 41520

American (AMR) AF: 0.0393 AC: 601 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.0737 AC: 256 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5186

South Asian (SAS) AF: 0.0222 AC: 107 AN: 4828

European-Finnish (FIN) AF: 0.0833 AC: 883 AN: 10594

Middle Eastern (MID) AF: 0.0408 AC: 12 AN: 294

European-Non Finnish (NFE) AF: 0.0603 AC: 4103 AN: 68008

Other (OTH) AF: 0.0455 AC: 96 AN: 2110

Alfa AF: 0.0526 Hom.: 24

Bravo AF: 0.0430

Asia WGS AF: 0.0120 AC: 41 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	4.7
DANN	Benign	0.86
PhyloP100		0.45
Mutation Taster		=100/0	polymorphism

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: rs9614781; hg19: chr22-46192942;