Variant 22-45718364-C-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 ENST00000252934.10(ATXN10):c.648-49C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.157 in 1,423,964 control chromosomes in the GnomAD database, including 18,777 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.17 ( 2578 hom., cov: 32)

Exomes 𝑓: 0.16 ( 16199 hom. )

Consequence

ATXN10
ENST00000252934.10 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.0840

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=-0.89).

BP6

Variant 22-45718364-C-T is Benign according to our data. Variant chr22-45718364-C-T is described in ClinVar as [Benign]. Clinvar id is 1232451.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.243 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein
ATXN10	NM_013236.4 linkuse as main transcript	c.648-49C>T	intron_variant	ENST00000252934.10	NP_037368.1
ATXN10	NM_001167621.2 linkuse as main transcript	c.456-49C>T	intron_variant		NP_001161093.1
ATXN10	XM_047441314.1 linkuse as main transcript	c.648-49C>T	intron_variant		XP_047297270.1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	Appris	UniProt
ATXN10	ENST00000252934.10 linkuse as main transcript	c.648-49C>T	intron_variant	1	NM_013236.4	ENSP00000252934	P1	Q9UBB4-1
ATXN10	ENST00000381061.8 linkuse as main transcript	c.456-49C>T	intron_variant	2		ENSP00000370449		Q9UBB4-2
ATXN10	ENST00000476998.5 linkuse as main transcript	n.127-49C>T	intron_variant, non_coding_transcript_variant	3
ATXN10	ENST00000498009.5 linkuse as main transcript	n.822-49C>T	intron_variant, non_coding_transcript_variant	5

Frequencies

GnomAD3 genomes

AF:

0.174

AC:

26506

AN:

151952

Hom.:

2563

Cov.:

show subpopulations

Gnomad AFR

AF:

0.246

Gnomad AMI

AF:

0.104

Gnomad AMR

AF:

0.134

Gnomad ASJ

AF:

0.221

Gnomad EAS

AF:

0.0558

Gnomad SAS

AF:

0.113

Gnomad FIN

AF:

0.141

Gnomad MID

AF:

0.180

Gnomad NFE

AF:

0.157

Gnomad OTH

AF:

0.176

GnomAD3 exomes

AF:

0.140

AC:

34984

AN:

250756

Hom.:

2802

AF XY:

0.141

AC XY:

19069

AN XY:

135560

show subpopulations

Gnomad AFR exome

AF:

0.244

Gnomad AMR exome

AF:

0.0839

Gnomad ASJ exome

AF:

0.211

Gnomad EAS exome

AF:

0.0491

Gnomad SAS exome

AF:

0.125

Gnomad FIN exome

AF:

0.144

Gnomad NFE exome

AF:

0.152

Gnomad OTH exome

AF:

0.162

GnomAD4 exome

AF:

0.155

AC:

197595

AN:

1271894

Hom.:

16199

Cov.:

AF XY:

0.155

AC XY:

99489

AN XY:

642948

show subpopulations

Gnomad4 AFR exome

AF:

0.257

Gnomad4 AMR exome

AF:

0.0896

Gnomad4 ASJ exome

AF:

0.211

Gnomad4 EAS exome

AF:

0.0725

Gnomad4 SAS exome

AF:

0.126

Gnomad4 FIN exome

AF:

0.144

Gnomad4 NFE exome

AF:

0.160

Gnomad4 OTH exome

AF:

0.164

GnomAD4 genome

AF:

0.175

AC:

26563

AN:

152070

Hom.:

2578

Cov.:

AF XY:

0.173

AC XY:

12894

AN XY:

74330

show subpopulations

Gnomad4 AFR

AF:

0.247

Gnomad4 AMR

AF:

0.134

Gnomad4 ASJ

AF:

0.221

Gnomad4 EAS

AF:

0.0557

Gnomad4 SAS

AF:

0.113

Gnomad4 FIN

AF:

0.141

Gnomad4 NFE

AF:

0.157

Gnomad4 OTH

AF:

0.176

Alfa

AF:

0.163

Hom.:

2612

Bravo

AF:

0.176

Asia WGS

AF:

0.0920

AC:

321

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	clinical testing	GeneDx	Jun 18, 2021	- -
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

1.0

DANN

Benign

0.19

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