Variant 22-45718518-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.14

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 -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	Effect	MANE	Protein
ATXN10	NM_013236.4 linkuse as main transcript	c.728+25G>T	intron_variant	ENST00000252934.10	NP_037368.1
ATXN10	NM_001167621.2 linkuse as main transcript	c.536+25G>T	intron_variant		NP_001161093.1
ATXN10	XM_047441314.1 linkuse as main transcript	c.728+25G>T	intron_variant		XP_047297270.1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	Appris	UniProt
ATXN10	ENST00000252934.10 linkuse as main transcript	c.728+25G>T	intron_variant	1	NM_013236.4	ENSP00000252934	P1	Q9UBB4-1
ATXN10	ENST00000381061.8 linkuse as main transcript	c.536+25G>T	intron_variant	2		ENSP00000370449		Q9UBB4-2
ATXN10	ENST00000476998.5 linkuse as main transcript	n.207+25G>T	intron_variant, non_coding_transcript_variant	3
ATXN10	ENST00000483549.5 linkuse as main transcript	n.71+25G>T	intron_variant, non_coding_transcript_variant	2

Frequencies

GnomAD3 genomes

AF:

0.414

AC:

62823

AN:

151866

Hom.:

14588

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.337

AC XY:

242514

AN XY:

718964

show subpopulations

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.:

AF XY:

0.410

AC XY:

30426

AN XY:

74278

show subpopulations

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:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
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

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