rs9614781

chr22-45797062-C-G

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ATXN10	NM_013236.4	c.1174-9897C>G		intron_variant		ENST00000252934.10
ATXN10	NM_001167621.2	c.982-9897C>G		intron_variant
ATXN10	XM_047441314.1	c.1174-9897C>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ATXN10	ENST00000252934.10	c.1174-9897C>G		intron_variant		1	NM_013236.4	P1

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

Gnomad4 AFR AF: 0.0255

Gnomad4 AMR AF: 0.0393

Gnomad4 ASJ AF: 0.0737

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.0222

Gnomad4 FIN AF: 0.0833

Gnomad4 NFE AF: 0.0603

Gnomad4 OTH AF: 0.0455

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	4.7
Dann	Benign	0.86

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

Publications

LitVar

Other links and lift over

dbSNP: rs9614781; hg19: chr22-46192942;