22-45718518-G-T

Variant names:

• chr22-45718518-G-T
• rs138156
• NM_013236.4:c.728+25G>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong 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, multiple submitters, no conflicts B:2
• 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

Our verdict: Benign. The variant received -20 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_multiple_submitters_no_conflicts, 2 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 rank	MANE	Protein	UniProt
ATXN10	NM_013236.4	c.728+25G>T		intron_variant	Intron 6 of 11	ENST00000252934.10	NP_037368.1
ATXN10	NM_001167621.2	c.536+25G>T		intron_variant	Intron 5 of 10		NP_001161093.1
ATXN10	XM_047441314.1	c.728+25G>T		intron_variant	Intron 6 of 11		XP_047297270.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATXN10	ENST00000252934.10	c.728+25G>T		intron_variant	Intron 6 of 11	1	NM_013236.4	ENSP00000252934.4

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

GnomAD2 exomes AF: 0.329 AC: 82547 AN: 250626 AF XY: 0.324

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 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 AC: 21814 AN: 33098

Gnomad4 AMR exome AF: 0.265 AC: 11840 AN: 44646

Gnomad4 ASJ exome AF: 0.365 AC: 9490 AN: 26000

Gnomad4 EAS exome AF: 0.344 AC: 13629 AN: 39578

Gnomad4 SAS exome AF: 0.275 AC: 23635 AN: 85794

Gnomad4 FIN exome AF: 0.327 AC: 17436 AN: 53382

Gnomad4 NFE exome AF: 0.337 AC: 369221 AN: 1094808

Gnomad4 Remaining exome AF: 0.354 AC: 21146 AN: 59778

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 AC: 0.644419 AN: 0.644419

Gnomad4 AMR AF: 0.304 AC: 0.304319 AN: 0.304319

Gnomad4 ASJ AF: 0.381 AC: 0.381268 AN: 0.381268

Gnomad4 EAS AF: 0.277 AC: 0.277477 AN: 0.277477

Gnomad4 SAS AF: 0.270 AC: 0.269502 AN: 0.269502

Gnomad4 FIN AF: 0.324 AC: 0.32373 AN: 0.32373

Gnomad4 NFE AF: 0.337 AC: 0.337145 AN: 0.337145

Gnomad4 OTH AF: 0.379 AC: 0.378802 AN: 0.378802

Alfa AF: 0.364 Hom.: 5384

Bravo AF: 0.422

Asia WGS AF: 0.278 AC: 967 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Nov 10, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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
Mutation Taster		=100/0	polymorphism (auto)

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;