22-45671813-C-G

Variant names:

• chr22-45671813-C-G
• rs144270457
• ENST00000381061.8:c.-251C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The ENST00000381061.8(ATXN10):​c.-251C>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ATXN10 ENST00000381061.8 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.29
• Publications: 1 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

ENSG00000280383 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.31).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000381061.8. 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.-251C>G		upstream_gene	N/A	NP_037368.1	Q9UBB4-1
	ATXN10	NM_001167621.2		c.-251C>G		upstream_gene	N/A	NP_001161093.1	Q9UBB4-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATXN10	ENST00000381061.8	TSL:2	c.-251C>G		5_prime_UTR	Exon 1 of 11	ENSP00000370449.4	Q9UBB4-2
	ENSG00000280383	ENST00000623075.1	TSL:6	n.14795C>G		non_coding_transcript_exon	Exon 1 of 1
	ATXN10	ENST00000252934.10	TSL:1 MANE Select	c.-251C>G		upstream_gene	N/A	ENSP00000252934.4	Q9UBB4-1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 180260 Hom.: 0 Cov.: 2 AF XY: 0.00 AC XY: 0 AN XY: 94500

African (AFR) AF: 0.00 AC: 0 AN: 4086

American (AMR) AF: 0.00 AC: 0 AN: 4282

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 5880

East Asian (EAS) AF: 0.00 AC: 0 AN: 12874

South Asian (SAS) AF: 0.00 AC: 0 AN: 15346

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 13114

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 912

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 112684

Other (OTH) AF: 0.00 AC: 0 AN: 11082

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 13

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.31
CADD	Benign	9.8
DANN	Benign	0.83
PhyloP100		-1.3
PromoterAI		-0.61	Under-expression

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: rs144270457; hg19: chr22-46067693;