22-45718267-C-T

Position:

• chr22-45718267-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The ENST00000252934.10(ATXN10):​c.648-146C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.172 in 732,102 control chromosomes in the GnomAD database, including 12,074 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.14 (1978 hom., cov: 32)
  • Exomes 𝑓: 0.18 (10096 hom.)
• Consequence: ATXN10 ENST00000252934.10 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.549

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 22-45718267-C-T is Benign according to our data. Variant chr22-45718267-C-T is described in ClinVar as [Benign]. Clinvar id is 1296745.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.213 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATXN10	NM_013236.4	c.648-146C>T		intron_variant		ENST00000252934.10	NP_037368.1
ATXN10	NM_001167621.2	c.456-146C>T		intron_variant			NP_001161093.1
ATXN10	XM_047441314.1	c.648-146C>T		intron_variant			XP_047297270.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ATXN10	ENST00000252934.10	c.648-146C>T		intron_variant		1	NM_013236.4	ENSP00000252934	P1
ATXN10	ENST00000381061.8	c.456-146C>T		intron_variant		2		ENSP00000370449
ATXN10	ENST00000476998.5	n.127-146C>T		intron_variant, non_coding_transcript_variant		3
ATXN10	ENST00000498009.5	n.822-146C>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.142 AC: 21633 AN: 151848 Hom.: 1976 Cov.: 32

Gnomad AFR AF: 0.0363

Gnomad AMI AF: 0.239

Gnomad AMR AF: 0.133

Gnomad ASJ AF: 0.147

Gnomad EAS AF: 0.223

Gnomad SAS AF: 0.147

Gnomad FIN AF: 0.220

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.190

Gnomad OTH AF: 0.137

GnomAD4 exome AF: 0.180 AC: 104552 AN: 580136 Hom.: 10096 AF XY: 0.178 AC XY: 56133 AN XY: 314802

Gnomad4 AFR exome AF: 0.0343

Gnomad4 AMR exome AF: 0.143

Gnomad4 ASJ exome AF: 0.139

Gnomad4 EAS exome AF: 0.279

Gnomad4 SAS exome AF: 0.136

Gnomad4 FIN exome AF: 0.216

Gnomad4 NFE exome AF: 0.187

Gnomad4 OTH exome AF: 0.167

GnomAD4 genome AF: 0.142 AC: 21637 AN: 151966 Hom.: 1978 Cov.: 32 AF XY: 0.144 AC XY: 10684 AN XY: 74262

Gnomad4 AFR AF: 0.0362

Gnomad4 AMR AF: 0.133

Gnomad4 ASJ AF: 0.147

Gnomad4 EAS AF: 0.223

Gnomad4 SAS AF: 0.147

Gnomad4 FIN AF: 0.220

Gnomad4 NFE AF: 0.190

Gnomad4 OTH AF: 0.136

Alfa AF: 0.179 Hom.: 359

Bravo AF: 0.132

Asia WGS AF: 0.157 AC: 543 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 10, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.9
DANN	Benign	0.44

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: rs2071851; hg19: chr22-46114147;