Variant 22-45729448-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_013236.4(ATXN10):c.752T>C(p.Ile251Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00000274 in 1,461,874 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

ATXN10
NM_013236.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.43

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 Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.33002305).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
ATXN10	NM_013236.4 linkuse as main transcript	c.752T>C	p.Ile251Thr	missense_variant	7/12	ENST00000252934.10
ATXN10	NM_001167621.2 linkuse as main transcript	c.560T>C	p.Ile187Thr	missense_variant	6/11
ATXN10	XM_047441314.1 linkuse as main transcript	c.752T>C	p.Ile251Thr	missense_variant	7/12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ATXN10	ENST00000252934.10 linkuse as main transcript	c.752T>C	p.Ile251Thr	missense_variant	7/12	1	NM_013236.4	P1	Q9UBB4-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000274

AC:

AN:

1461874

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727240

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000374

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 03, 2022

The c.752T>C (p.I251T) alteration is located in exon 7 (coding exon 7) of the ATXN10 gene. This alteration results from a T to C substitution at nucleotide position 752, causing the isoleucine (I) at amino acid position 251 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Uncertain

0.14

BayesDel_noAF

Uncertain

-0.040

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.15

.;T;.;.

Eigen

Benign

-0.27

Eigen_PC

Benign

-0.17

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.85

D;T;T;T

M_CAP

Benign

0.014

MetaRNN

Benign

0.33

T;T;T;T

MetaSVM

Benign

-0.89

MutationAssessor

Uncertain

2.3

.;M;.;.

MutationTaster

Benign

0.89

D;D

PrimateAI

Uncertain

0.56

PROVEAN

Benign

-1.8

N;N;.;N

REVEL

Benign

0.20

Sift

Benign

0.050

D;D;.;D

Sift4G

Uncertain

0.012

D;D;.;D

Polyphen

0.087

.;B;.;.

Vest4

0.58

MutPred

0.55

.;Loss of stability (P = 0.0116);Loss of stability (P = 0.0116);.;

MVP

0.40

MPC

0.053

ClinPred

0.46

GERP RS

5.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.084

gMVP

0.10

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