dbSNP rs136002: ATXN10:c.1174-13649G>A (chr22-45793310-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_013236.4(ATXN10):c.1174-13649G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.853 in 171,808 control chromosomes in the GnomAD database, including 62,791 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.86 ( 56015 hom., cov: 32)

Exomes 𝑓: 0.83 ( 6776 hom. )

Consequence

ATXN10
NM_013236.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.01

Publications

5 publications found

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:

TRNT1P2 (HGNC:56782): (TRNT1 pseudogene 2)

TRNT1P2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.97).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.924 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
ATXN10	NM_013236.4 link	c.1174-13649G>A	intron_variant	Intron 9 of 11	ENST00000252934.10	NP_037368.1	Q9UBB4-1
TRNT1P2		n.45793310G>A	intragenic_variant
ATXN10	NM_001167621.2 link	c.982-13649G>A	intron_variant	Intron 8 of 10		NP_001161093.1	Q9UBB4-2
ATXN10	XM_047441314.1 link	c.1174-13649G>A	intron_variant	Intron 9 of 11		XP_047297270.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATXN10	ENST00000252934.10 link	c.1174-13649G>A		intron_variant	Intron 9 of 11	1	NM_013236.4	ENSP00000252934.4		Q9UBB4-1

Frequencies

GnomAD3 genomes

AF:

0.856

AC:

130206

AN:

152078

Hom.:

55953

Cov.:

show subpopulations

Gnomad AFR

AF:

0.931

Gnomad AMI

AF:

0.789

Gnomad AMR

AF:

0.861

Gnomad ASJ

AF:

0.850

Gnomad EAS

AF:

0.789

Gnomad SAS

AF:

0.845

Gnomad FIN

AF:

0.832

Gnomad MID

AF:

0.896

Gnomad NFE

AF:

0.820

Gnomad OTH

AF:

0.864

GnomAD4 exome

AF:

0.831

AC:

16303

AN:

19612

Hom.:

6776

Cov.:

AF XY:

0.833

AC XY:

8277

AN XY:

9942

show subpopulations

African (AFR)

AF:

0.927

AC:

532

AN:

574

American (AMR)

AF:

0.811

AC:

532

AN:

656

Ashkenazi Jewish (ASJ)

AF:

0.844

AC:

559

AN:

662

East Asian (EAS)

AF:

0.697

AC:

619

AN:

888

South Asian (SAS)

AF:

0.829

AC:

378

AN:

456

European-Finnish (FIN)

AF:

0.932

AC:

1849

AN:

1984

Middle Eastern (MID)

AF:

0.875

AC:

1438

AN:

1644

European-Non Finnish (NFE)

AF:

0.813

AC:

9434

AN:

11606

Other (OTH)

AF:

0.842

AC:

962

AN:

1142

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.510

Heterozygous variant carriers

140

279

419

558

698

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

172

258

344

430

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.856

AC:

130326

AN:

152196

Hom.:

56015

Cov.:

AF XY:

0.857

AC XY:

63733

AN XY:

74402

show subpopulations

African (AFR)

AF:

0.931

AC:

38691

AN:

41542

American (AMR)

AF:

0.861

AC:

13169

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.850

AC:

2948

AN:

3470

East Asian (EAS)

AF:

0.788

AC:

4079

AN:

5174

South Asian (SAS)

AF:

0.845

AC:

4068

AN:

4814

European-Finnish (FIN)

AF:

0.832

AC:

8807

AN:

10584

Middle Eastern (MID)

AF:

0.884

AC:

260

AN:

294

European-Non Finnish (NFE)

AF:

0.820

AC:

55758

AN:

68006

Other (OTH)

AF:

0.865

AC:

1826

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

973

1946

2918

3891

4864

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

890

1780

2670

3560

4450

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.824

Hom.:

25038

Bravo

AF:

0.862

Asia WGS

AF:

0.835

AC:

2904

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.97

CADD

Benign

0.53

(source)

DANN

Benign

0.32

PhyloP100

2.0

PromoterAI

-0.0062

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over