rs5764850

Positions:

• chr22-45794157-A-C
• chr22-45794157-A-T

Variant summary

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

The NM_013236.4(ATXN10):​c.1174-12802A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.579 in 151,966 control chromosomes in the GnomAD database, including 26,675 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 0.58 (26675 hom., cov: 31)
• Consequence: ATXN10 NM_013236.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.502

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=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.732 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATXN10	NM_013236.4	c.1174-12802A>C		intron_variant		ENST00000252934.10	NP_037368.1
ATXN10	NM_001167621.2	c.982-12802A>C		intron_variant			NP_001161093.1
ATXN10	XM_047441314.1	c.1174-12802A>C		intron_variant			XP_047297270.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ATXN10	ENST00000252934.10	c.1174-12802A>C		intron_variant		1	NM_013236.4	ENSP00000252934	P1

Frequencies

GnomAD3 genomes AF: 0.580 AC: 88035 AN: 151848 Hom.: 26669 Cov.: 31

Gnomad AFR AF: 0.387

Gnomad AMI AF: 0.630

Gnomad AMR AF: 0.698

Gnomad ASJ AF: 0.615

Gnomad EAS AF: 0.752

Gnomad SAS AF: 0.723

Gnomad FIN AF: 0.650

Gnomad MID AF: 0.661

Gnomad NFE AF: 0.632

Gnomad OTH AF: 0.620

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

GnomAD4 genome AF: 0.579 AC: 88058 AN: 151966 Hom.: 26675 Cov.: 31 AF XY: 0.584 AC XY: 43382 AN XY: 74282

Gnomad4 AFR AF: 0.387

Gnomad4 AMR AF: 0.698

Gnomad4 ASJ AF: 0.615

Gnomad4 EAS AF: 0.752

Gnomad4 SAS AF: 0.723

Gnomad4 FIN AF: 0.650

Gnomad4 NFE AF: 0.632

Gnomad4 OTH AF: 0.624

Alfa AF: 0.462 Hom.: 1288

Bravo AF: 0.576

Asia WGS AF: 0.725 AC: 2521 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	2.0
DANN	Benign	0.67

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: rs5764850; hg19: chr22-46190037;