Genetic Variant ATXN10:c.116+4A>T (chr22-45672183-A-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_013236.4(ATXN10):c.116+4A>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

ATXN10
NM_013236.4 splice_region, intron

Scores

Splicing: ADA: 0.9606

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.310

Publications

0 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 Gene-Disease associations (from GenCC):

spinocerebellar ataxia type 10
Inheritance: AD Classification: STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet

ATXN10 links:

ENSG00000280383 (HGNC:):

ENSG00000280383 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.54).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_013236.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATXN10	NM_013236.4	MANE Select	c.116+4A>T		splice_region intron	N/A	NP_037368.1	Q9UBB4-1
	ATXN10	NM_001167621.2		c.116+4A>T		splice_region intron	N/A	NP_001161093.1	Q9UBB4-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ATXN10	ENST00000252934.10	TSL:1 MANE Select	c.116+4A>T	splice_region intron	N/A	ENSP00000252934.4	Q9UBB4-1
ATXN10	ENST00000381061.8	TSL:2	c.116+4A>T	splice_region intron	N/A	ENSP00000370449.4	Q9UBB4-2
ENSG00000280383	ENST00000623075.1	TSL:6	n.15165A>T	non_coding_transcript_exon	Exon 1 of 1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1377092

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

679554

African (AFR)

AF:

0.00

AC:

AN:

30448

American (AMR)

AF:

0.00

AC:

AN:

35162

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24598

East Asian (EAS)

AF:

0.00

AC:

AN:

34952

South Asian (SAS)

AF:

0.00

AC:

AN:

78334

European-Finnish (FIN)

AF:

0.00

AC:

AN:

39870

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4366

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1072366

Other (OTH)

AF:

0.00

AC:

AN:

56996

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions as Germline

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Spinocerebellar ataxia type 10 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.54

CADD

Benign

(source)

DANN

Benign

0.94

PhyloP100

0.31

PromoterAI

-0.18

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Pathogenic

0.96

dbscSNV1_RF

Benign

0.62

SpliceAI score (max)

0.050

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over