22-45718518-G-T

Variant summary

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

The NM_013236.4(ATXN10):c.728+25G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.347 in 1,594,808 control chromosomes in the GnomAD database, including 100,704 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.41 (14627 hom., cov: 31)
  • Exomes 𝑓: 0.34 (86077 hom.)
• Consequence: ATXN10 NM_013236.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.14

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=-0.76).
• BP6: Variant 22-45718518-G-T is Benign according to our data. Variant chr22-45718518-G-T is described in ClinVar as [Benign]. Clinvar id is 1250676.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.638 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ATXN10	NM_013236.4	c.728+25G>T		intron_variant		ENST00000252934.10
ATXN10	NM_001167621.2	c.536+25G>T		intron_variant
ATXN10	XM_047441314.1	c.728+25G>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ATXN10	ENST00000252934.10	c.728+25G>T		intron_variant		1	NM_013236.4	P1
ATXN10	ENST00000381061.8	c.536+25G>T		intron_variant		2
ATXN10	ENST00000476998.5	n.207+25G>T		intron_variant, non_coding_transcript_variant		3
ATXN10	ENST00000483549.5	n.71+25G>T		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.414 AC: 62823 AN: 151866 Hom.: 14588 Cov.: 31

Gnomad AFR AF: 0.644

Gnomad AMI AF: 0.321

Gnomad AMR AF: 0.305

Gnomad ASJ AF: 0.381

Gnomad EAS AF: 0.277

Gnomad SAS AF: 0.269

Gnomad FIN AF: 0.324

Gnomad MID AF: 0.320

Gnomad NFE AF: 0.337

Gnomad OTH AF: 0.382

GnomAD3 exomes AF: 0.329 AC: 82547 AN: 250626 Hom.: 14735 AF XY: 0.324 AC XY: 43865 AN XY: 135570

Gnomad AFR exome AF: 0.655

Gnomad AMR exome AF: 0.258

Gnomad ASJ exome AF: 0.363

Gnomad EAS exome AF: 0.257

Gnomad SAS exome AF: 0.276

Gnomad FIN exome AF: 0.330

Gnomad NFE exome AF: 0.328

Gnomad OTH exome AF: 0.334

GnomAD4 exome AF: 0.340 AC: 490337 AN: 1442824 Hom.: 86077 Cov.: 29 AF XY: 0.337 AC XY: 242514 AN XY: 718964

Gnomad4 AFR exome AF: 0.659

Gnomad4 AMR exome AF: 0.265

Gnomad4 ASJ exome AF: 0.365

Gnomad4 EAS exome AF: 0.344

Gnomad4 SAS exome AF: 0.275

Gnomad4 FIN exome AF: 0.327

Gnomad4 NFE exome AF: 0.337

Gnomad4 OTH exome AF: 0.354

GnomAD4 genome AF: 0.414 AC: 62919 AN: 151984 Hom.: 14627 Cov.: 31 AF XY: 0.410 AC XY: 30426 AN XY: 74278

Gnomad4 AFR AF: 0.644

Gnomad4 AMR AF: 0.304

Gnomad4 ASJ AF: 0.381

Gnomad4 EAS AF: 0.277

Gnomad4 SAS AF: 0.270

Gnomad4 FIN AF: 0.324

Gnomad4 NFE AF: 0.337

Gnomad4 OTH AF: 0.379

Alfa AF: 0.363 Hom.: 3609

Bravo AF: 0.422

Asia WGS AF: 0.278 AC: 967 AN: 3478

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	-0.76
CADD	Benign	5.9
DANN	Benign	0.48
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs138156; hg19: chr22-46114398; COSMIC: COSV53294235; COSMIC: COSV53294235;