Variant 22-45672094-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_013236.4(ATXN10):c.31C>A(p.Leu11Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000221 in 1,539,138 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00016 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000072 ( 0 hom. )

Consequence

ATXN10
NM_013236.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.24

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 Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.046641022).

BS2

High AC in GnomAd4 at 24 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
ATXN10	NM_013236.4 linkuse as main transcript	c.31C>A	p.Leu11Met	missense_variant	1/12	ENST00000252934.10	NP_037368.1
ATXN10	NM_001167621.2 linkuse as main transcript	c.31C>A	p.Leu11Met	missense_variant	1/11		NP_001161093.1
ATXN10	XM_047441314.1 linkuse as main transcript	c.31C>A	p.Leu11Met	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.31C>A	p.Leu11Met	missense_variant	1/12	1	NM_013236.4	ENSP00000252934	P1	Q9UBB4-1
	ENST00000623075.1 linkuse as main transcript	n.15076C>A		non_coding_transcript_exon_variant	1/1
ATXN10	ENST00000381061.8 linkuse as main transcript	c.31C>A	p.Leu11Met	missense_variant	1/11	2		ENSP00000370449		Q9UBB4-2

Frequencies

GnomAD3 genomes

AF:

0.000158

AC:

AN:

152068

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000579

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000145

AC:

AN:

137718

Hom.:

AF XY:

0.0000133

AC XY:

AN XY:

74942

show subpopulations

Gnomad AFR exome

AF:

0.000308

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000721

AC:

AN:

1386952

Hom.:

Cov.:

AF XY:

0.00000730

AC XY:

AN XY:

684474

show subpopulations

Gnomad4 AFR exome

AF:

0.000318

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.000158

AC:

AN:

152186

Hom.:

Cov.:

AF XY:

0.000148

AC XY:

AN XY:

74418

show subpopulations

Gnomad4 AFR

AF:

0.000578

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.000132

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

Aug 09, 2021

The c.31C>A (p.L11M) alteration is located in exon 1 (coding exon 1) of the ATXN10 gene. This alteration results from a C to A substitution at nucleotide position 31, causing the leucine (L) at amino acid position 11 to be replaced by a methionine (M). 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

0.16

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.51

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.10

.;T;.

Eigen

Benign

-0.55

Eigen_PC

Benign

-0.59

FATHMM_MKL

Benign

0.11

LIST_S2

Benign

0.50

T;T;T

M_CAP

Benign

0.058

MetaRNN

Benign

0.047

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-0.69

N;N;.

MutationTaster

Benign

1.0

N;N

PrimateAI

Pathogenic

0.89

PROVEAN

Benign

-0.62

N;N;.

REVEL

Benign

0.035

Sift

Uncertain

0.017

D;D;.

Sift4G

Pathogenic

0.0

D;T;.

Polyphen

0.062

.;B;.

Vest4

0.14

MutPred

0.32

Gain of catalytic residue at L11 (P = 0.0574);Gain of catalytic residue at L11 (P = 0.0574);Gain of catalytic residue at L11 (P = 0.0574);

MVP

0.16

MPC

0.034

ClinPred

0.13

GERP RS

0.65

Varity_R

0.084

gMVP

0.25

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