chr22-45796515-T-C

Variant names:

• chr22-45796515-T-C
• rs136005
• NM_013236.4:c.1174-10444T>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.1174-10444T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.947 in 152,266 control chromosomes in the GnomAD database, including 68,374 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 0.95 (68374 hom., cov: 32)
• Consequence: ATXN10 NM_013236.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.999
• 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=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.978 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.1174-10444T>C		intron	N/A	NP_037368.1	Q9UBB4-1
	ATXN10	NM_001167621.2		c.982-10444T>C		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.1174-10444T>C		intron	N/A	ENSP00000252934.4	Q9UBB4-1
	ATXN10	ENST00000381061.8	TSL:2	c.982-10444T>C		intron	N/A	ENSP00000370449.4	Q9UBB4-2
	ATXN10	ENST00000435026.5	TSL:3	c.430-10444T>C		intron	N/A	ENSP00000391117.1	B1AHE4

Frequencies

GnomAD3 genomes AF: 0.947 AC: 144083 AN: 152148 Hom.: 68315 Cov.: 32

Gnomad AFR AF: 0.986

Gnomad AMI AF: 0.893

Gnomad AMR AF: 0.952

Gnomad ASJ AF: 0.913

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.978

Gnomad FIN AF: 0.945

Gnomad MID AF: 0.937

Gnomad NFE AF: 0.919

Gnomad OTH AF: 0.938

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

GnomAD4 genome AF: 0.947 AC: 144201 AN: 152266 Hom.: 68374 Cov.: 32 AF XY: 0.949 AC XY: 70673 AN XY: 74448

African (AFR) AF: 0.986 AC: 40988 AN: 41556

American (AMR) AF: 0.952 AC: 14562 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.913 AC: 3170 AN: 3472

East Asian (EAS) AF: 0.999 AC: 5178 AN: 5182

South Asian (SAS) AF: 0.978 AC: 4712 AN: 4818

European-Finnish (FIN) AF: 0.945 AC: 10039 AN: 10618

Middle Eastern (MID) AF: 0.929 AC: 273 AN: 294

European-Non Finnish (NFE) AF: 0.919 AC: 62479 AN: 68004

Other (OTH) AF: 0.939 AC: 1986 AN: 2116

Alfa AF: 0.928 Hom.: 8483

Bravo AF: 0.950

Asia WGS AF: 0.992 AC: 3451 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	1.8
DANN	Benign	0.34
PhyloP100		-1.0
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: rs136005; hg19: chr22-46192395;