Variant X-13319637-G-C details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001135995.2(ATXN3L):c.298C>G(p.Gln100Glu) variant causes a missense change. The variant allele was found at a frequency of 0.0000447 in 1,207,215 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 11 hemizygotes in GnomAD. 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 0.00028 ( 0 hom., 6 hem., cov: 23)

Exomes 𝑓: 0.000021 ( 0 hom. 5 hem. )

Consequence

ATXN3L
NM_001135995.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.78

Variant links:

Genes affected

ATXN3L (HGNC:24173): (ataxin 3 like) This intronless gene may be a pseudogene (PMID:11450850). This gene is similar to the multi-exon gene which encodes ataxin 3 and contains a coding region which could encode a protein similar to ataxin 3. Mutations in the gene encoding ataxin 3 are associated with Machado-Joseph disease. [provided by RefSeq, Sep 2011]

ATXN3L links:

GS1-600G8.3 (HGNC:):

GS1-600G8.3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.024434239).

BS2

High Hemizygotes in GnomAd4 at 6 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATXN3L	NM_001135995.2 linkuse as main transcript	c.298C>G	p.Gln100Glu	missense_variant	1/1	ENST00000380622.5	NP_001129467.1	Q9H3M9B4DYC7
ATXN3L	NM_001387036.1 linkuse as main transcript	c.234+64C>G		intron_variant			NP_001373965.1
GS1-600G8.3	NR_046087.1 linkuse as main transcript	n.1953G>C		non_coding_transcript_exon_variant	17/17

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ATXN3L	ENST00000380622.5 linkuse as main transcript	c.298C>G	p.Gln100Glu	missense_variant	1/1	6	NM_001135995.2	ENSP00000369996.2		Q9H3M9
GS1-600G8.3	ENST00000431486.1 linkuse as main transcript	n.1953G>C		non_coding_transcript_exon_variant	17/17	1

Frequencies

GnomAD3 genomes

AF:

0.000277

AC:

AN:

111977

Hom.:

Cov.:

AF XY:

0.000175

AC XY:

AN XY:

34205

show subpopulations

Gnomad AFR

AF:

0.00101

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:

0.0000773

AC:

AN:

181170

Hom.:

AF XY:

0.0000446

AC XY:

AN XY:

67334

show subpopulations

Gnomad AFR exome

AF:

0.000970

Gnomad AMR exome

AF:

0.0000730

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:

0.0000210

AC:

AN:

1095238

Hom.:

Cov.:

AF XY:

0.0000138

AC XY:

AN XY:

362178

show subpopulations

Gnomad4 AFR exome

AF:

0.000720

Gnomad4 AMR exome

AF:

0.0000568

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:

0.00000119

Gnomad4 OTH exome

AF:

0.0000218

GnomAD4 genome

AF:

0.000277

AC:

AN:

111977

Hom.:

Cov.:

AF XY:

0.000175

AC XY:

AN XY:

34205

show subpopulations

Gnomad4 AFR

AF:

0.00101

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

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.000298

ESP6500AA

AF:

0.000761

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000666

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 03, 2022

The c.298C>G (p.Q100E) alteration is located in exon 1 (coding exon 1) of the ATXN3L gene. This alteration results from a C to G substitution at nucleotide position 298, causing the glutamine (Q) at amino acid position 100 to be replaced by a glutamic acid (E). 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

0.12

BayesDel_addAF

Benign

-0.61

BayesDel_noAF

Benign

-0.70

CADD

Benign

DANN

Benign

0.50

DEOGEN2

Benign

0.0091

FATHMM_MKL

Benign

0.71

LIST_S2

Uncertain

0.95

M_CAP

Benign

0.0028

MetaRNN

Benign

0.024

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.4

PrimateAI

Benign

0.26

PROVEAN

Benign

-0.49

REVEL

Benign

0.13

Sift

Benign

0.28

Sift4G

Benign

0.40

Polyphen

0.053

Vest4

0.21

MVP

0.29

MPC

0.081

ClinPred

0.035

GERP RS

-0.22

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.20

gMVP

0.76

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