rs136005

Positions:

• chr22-45796515-T-C
• chr22-45796515-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000252934.10(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 ENST00000252934.10 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.999

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=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.978 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATXN10	NM_013236.4	c.1174-10444T>C		intron_variant		ENST00000252934.10	NP_037368.1
ATXN10	NM_001167621.2	c.982-10444T>C		intron_variant			NP_001161093.1
ATXN10	XM_047441314.1	c.1174-10444T>C		intron_variant			XP_047297270.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ATXN10	ENST00000252934.10	c.1174-10444T>C		intron_variant		1	NM_013236.4	ENSP00000252934	P1

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

Gnomad4 AFR AF: 0.986

Gnomad4 AMR AF: 0.952

Gnomad4 ASJ AF: 0.913

Gnomad4 EAS AF: 0.999

Gnomad4 SAS AF: 0.978

Gnomad4 FIN AF: 0.945

Gnomad4 NFE AF: 0.919

Gnomad4 OTH AF: 0.939

Alfa AF: 0.925 Hom.: 8101

Bravo AF: 0.950

Asia WGS AF: 0.992 AC: 3451 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	1.8
DANN	Benign	0.34

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: rs136005; hg19: chr22-46192395;