Variant 22-45729600-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The ENST00000252934.10(ATXN10):c.894+10G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00593 in 1,613,894 control chromosomes in the GnomAD database, including 38 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0044 ( 4 hom., cov: 32)

Exomes 𝑓: 0.0061 ( 34 hom. )

Consequence

ATXN10
ENST00000252934.10 intron

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:3

Conservation

PhyloP100: 0.514

Variant links:

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]

ATXN10 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BP6

Variant 22-45729600-G-T is Benign according to our data. Variant chr22-45729600-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 1285177.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr22-45729600-G-T is described in Lovd as [Likely_benign].

BS2

High AC in GnomAd4 at 673 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein
ATXN10	NM_013236.4 linkuse as main transcript	c.894+10G>T	intron_variant	ENST00000252934.10	NP_037368.1
ATXN10	NM_001167621.2 linkuse as main transcript	c.702+10G>T	intron_variant		NP_001161093.1
ATXN10	XM_047441314.1 linkuse as main transcript	c.894+10G>T	intron_variant		XP_047297270.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ATXN10	ENST00000252934.10 linkuse as main transcript	c.894+10G>T		intron_variant		1	NM_013236.4	ENSP00000252934	P1	Q9UBB4-1

Frequencies

GnomAD3 genomes

AF:

0.00444

AC:

675

AN:

152130

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00126

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00347

Gnomad ASJ

AF:

0.000576

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00186

Gnomad FIN

AF:

0.00359

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00756

Gnomad OTH

AF:

0.00335

GnomAD3 exomes

AF:

0.00423

AC:

1063

AN:

251280

Hom.:

AF XY:

0.00457

AC XY:

621

AN XY:

135804

show subpopulations

Gnomad AFR exome

AF:

0.000800

Gnomad AMR exome

AF:

0.00260

Gnomad ASJ exome

AF:

0.0000992

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00144

Gnomad FIN exome

AF:

0.00408

Gnomad NFE exome

AF:

0.00705

Gnomad OTH exome

AF:

0.00424

GnomAD4 exome

AF:

0.00608

AC:

8892

AN:

1461646

Hom.:

Cov.:

AF XY:

0.00614

AC XY:

4461

AN XY:

727124

show subpopulations

Gnomad4 AFR exome

AF:

0.000926

Gnomad4 AMR exome

AF:

0.00250

Gnomad4 ASJ exome

AF:

0.000191

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00169

Gnomad4 FIN exome

AF:

0.00428

Gnomad4 NFE exome

AF:

0.00722

Gnomad4 OTH exome

AF:

0.00560

GnomAD4 genome

AF:

0.00442

AC:

673

AN:

152248

Hom.:

Cov.:

AF XY:

0.00406

AC XY:

302

AN XY:

74456

show subpopulations

Gnomad4 AFR

AF:

0.00125

Gnomad4 AMR

AF:

0.00347

Gnomad4 ASJ

AF:

0.000576

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00186

Gnomad4 FIN

AF:

0.00359

Gnomad4 NFE

AF:

0.00753

Gnomad4 OTH

AF:

0.00331

Alfa

AF:

0.00521

Hom.:

Bravo

AF:

0.00413

Asia WGS

AF:

0.00144

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:3

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:3

Likely benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Likely benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

1.4

DANN

Benign

0.46

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over