Variant 22-45672142-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_013236.4(ATXN10):c.79C>T(p.Arg27Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000721 in 1,387,598 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 7.2e-7 ( 0 hom. )

Consequence

ATXN10
NM_013236.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.258

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:

(HGNC:):

links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
ATXN10	NM_013236.4 linkuse as main transcript	c.79C>T	p.Arg27Cys	missense_variant	1/12	ENST00000252934.10	NP_037368.1
ATXN10	NM_001167621.2 linkuse as main transcript	c.79C>T	p.Arg27Cys	missense_variant	1/11		NP_001161093.1
ATXN10	XM_047441314.1 linkuse as main transcript	c.79C>T	p.Arg27Cys	missense_variant	1/12		XP_047297270.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ATXN10	ENST00000252934.10 linkuse as main transcript	c.79C>T	p.Arg27Cys	missense_variant	1/12	1	NM_013236.4	ENSP00000252934	P1	Q9UBB4-1
	ENST00000623075.1 linkuse as main transcript	n.15124C>T		non_coding_transcript_exon_variant	1/1
ATXN10	ENST00000381061.8 linkuse as main transcript	c.79C>T	p.Arg27Cys	missense_variant	1/11	2		ENSP00000370449		Q9UBB4-2
ATXN10	ENST00000498009.5 linkuse as main transcript			upstream_gene_variant		5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.21e-7

AC:

AN:

1387598

Hom.:

Cov.:

AF XY:

0.00000146

AC XY:

AN XY:

684712

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:

0.00

Gnomad4 NFE exome

AF:

9.28e-7

Gnomad4 OTH exome

AF:

0.00

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

Sep 27, 2021

The c.79C>T (p.R27C) alteration is located in exon 1 (coding exon 1) of the ATXN10 gene. This alteration results from a C to T substitution at nucleotide position 79, causing the arginine (R) at amino acid position 27 to be replaced by a cysteine (C). 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

Pathogenic

0.97

BayesDel_addAF

Benign

-0.083

BayesDel_noAF

Benign

-0.36

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.18

.;T;.

Eigen

Benign

0.022

Eigen_PC

Benign

-0.041

FATHMM_MKL

Benign

0.042

LIST_S2

Uncertain

0.90

D;D;D

M_CAP

Pathogenic

0.89

MetaRNN

Uncertain

0.46

T;T;T

MetaSVM

Benign

-0.94

MutationAssessor

Benign

1.0

L;L;.

MutationTaster

Benign

1.0

D;N

PrimateAI

Pathogenic

0.95

PROVEAN

Benign

-0.29

N;N;.

REVEL

Benign

0.27

Sift

Uncertain

0.0010

D;D;.

Sift4G

Uncertain

0.026

D;D;.

Polyphen

1.0

.;D;.

Vest4

0.30

MutPred

0.67

Loss of disorder (P = 0.0306);Loss of disorder (P = 0.0306);Loss of disorder (P = 0.0306);

MVP

0.52

MPC

0.27

ClinPred

0.67

GERP RS

0.60

Varity_R

0.21

gMVP

0.28

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over