chr22-45796720-A-T

Variant names:

• chr22-45796720-A-T
• rs9614518
• NM_013236.4:c.1174-10239A>T

Variant summary

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

The NM_013236.4(ATXN10):​c.1174-10239A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0579 in 152,214 control chromosomes in the GnomAD database, including 277 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 0.058 (277 hom., cov: 33)
• Consequence: ATXN10 NM_013236.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.853
• 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: Labcorp Genetics (formerly Invitae), Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0617 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATXN10	NM_013236.4	MANE Select	c.1174-10239A>T		intron	N/A	NP_037368.1	Q9UBB4-1
	ATXN10	NM_001167621.2		c.982-10239A>T		intron	N/A	NP_001161093.1	Q9UBB4-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATXN10	ENST00000252934.10	TSL:1 MANE Select	c.1174-10239A>T		intron	N/A	ENSP00000252934.4	Q9UBB4-1
	ATXN10	ENST00000381061.8	TSL:2	c.982-10239A>T		intron	N/A	ENSP00000370449.4	Q9UBB4-2
	ATXN10	ENST00000435026.5	TSL:3	c.430-10239A>T		intron	N/A	ENSP00000391117.1	B1AHE4

Frequencies

GnomAD3 genomes AF: 0.0579 AC: 8808 AN: 152096 Hom.: 276 Cov.: 33

Gnomad AFR AF: 0.0638

Gnomad AMI AF: 0.0362

Gnomad AMR AF: 0.0429

Gnomad ASJ AF: 0.0738

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0212

Gnomad FIN AF: 0.0839

Gnomad MID AF: 0.0446

Gnomad NFE AF: 0.0604

Gnomad OTH AF: 0.0530

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

GnomAD4 genome AF: 0.0579 AC: 8819 AN: 152214 Hom.: 277 Cov.: 33 AF XY: 0.0585 AC XY: 4356 AN XY: 74434

African (AFR) AF: 0.0638 AC: 2648 AN: 41534

American (AMR) AF: 0.0428 AC: 655 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0738 AC: 256 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5182

South Asian (SAS) AF: 0.0220 AC: 106 AN: 4816

European-Finnish (FIN) AF: 0.0839 AC: 889 AN: 10602

Middle Eastern (MID) AF: 0.0445 AC: 13 AN: 292

European-Non Finnish (NFE) AF: 0.0604 AC: 4106 AN: 68000

Other (OTH) AF: 0.0529 AC: 112 AN: 2116

Alfa AF: 0.0177 Hom.: 8

Bravo AF: 0.0554

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.98
DANN	Benign	0.78
PhyloP100		-0.85
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: rs9614518; hg19: chr22-46192600;