X-13318940-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001135995.2(ATXN3L):​c.995G>A​(p.Gly332Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.405 in 1,208,315 control chromosomes in the GnomAD database, including 76,102 homozygotes. There are 160,490 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.51 ( 11769 hom., 16734 hem., cov: 23)
Exomes 𝑓: 0.39 ( 64333 hom. 143756 hem. )

Consequence

ATXN3L
NM_001135995.2 missense

Scores

16

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.153
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=1.0593325E-6).
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.811 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
ATXN3LNM_001135995.2 linkuse as main transcriptc.995G>A p.Gly332Asp missense_variant 1/1 ENST00000380622.5 NP_001129467.1 Q9H3M9B4DYC7
ATXN3LNM_001387036.1 linkuse as main transcriptc.731G>A p.Gly244Asp missense_variant 2/2 NP_001373965.1
GS1-600G8.3NR_046087.1 linkuse as main transcriptn.1449-68C>T intron_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
ATXN3LENST00000380622.5 linkuse as main transcriptc.995G>A p.Gly332Asp missense_variant 1/16 NM_001135995.2 ENSP00000369996.2 Q9H3M9
GS1-600G8.3ENST00000431486.1 linkuse as main transcriptn.1449-68C>T intron_variant 1

Frequencies

GnomAD3 genomes
AF:
0.508
AC:
56172
AN:
110634
Hom.:
11751
Cov.:
23
AF XY:
0.508
AC XY:
16677
AN XY:
32852
show subpopulations
Gnomad AFR
AF:
0.767
Gnomad AMI
AF:
0.232
Gnomad AMR
AF:
0.648
Gnomad ASJ
AF:
0.344
Gnomad EAS
AF:
0.836
Gnomad SAS
AF:
0.536
Gnomad FIN
AF:
0.362
Gnomad MID
AF:
0.369
Gnomad NFE
AF:
0.336
Gnomad OTH
AF:
0.513
GnomAD3 exomes
AF:
0.495
AC:
89477
AN:
180865
Hom.:
17332
AF XY:
0.471
AC XY:
31697
AN XY:
67283
show subpopulations
Gnomad AFR exome
AF:
0.775
Gnomad AMR exome
AF:
0.775
Gnomad ASJ exome
AF:
0.349
Gnomad EAS exome
AF:
0.824
Gnomad SAS exome
AF:
0.541
Gnomad FIN exome
AF:
0.363
Gnomad NFE exome
AF:
0.333
Gnomad OTH exome
AF:
0.448
GnomAD4 exome
AF:
0.395
AC:
433297
AN:
1097631
Hom.:
64333
Cov.:
34
AF XY:
0.396
AC XY:
143756
AN XY:
363233
show subpopulations
Gnomad4 AFR exome
AF:
0.777
Gnomad4 AMR exome
AF:
0.763
Gnomad4 ASJ exome
AF:
0.346
Gnomad4 EAS exome
AF:
0.861
Gnomad4 SAS exome
AF:
0.539
Gnomad4 FIN exome
AF:
0.360
Gnomad4 NFE exome
AF:
0.342
Gnomad4 OTH exome
AF:
0.425
GnomAD4 genome
AF:
0.508
AC:
56244
AN:
110684
Hom.:
11769
Cov.:
23
AF XY:
0.508
AC XY:
16734
AN XY:
32912
show subpopulations
Gnomad4 AFR
AF:
0.768
Gnomad4 AMR
AF:
0.649
Gnomad4 ASJ
AF:
0.344
Gnomad4 EAS
AF:
0.836
Gnomad4 SAS
AF:
0.537
Gnomad4 FIN
AF:
0.362
Gnomad4 NFE
AF:
0.336
Gnomad4 OTH
AF:
0.520
Alfa
AF:
0.382
Hom.:
30880
Bravo
AF:
0.547
TwinsUK
AF:
0.351
AC:
1303
ALSPAC
AF:
0.345
AC:
998
ESP6500AA
AF:
0.762
AC:
2003
ESP6500EA
AF:
0.339
AC:
1862
ExAC
AF:
0.478
AC:
57598
EpiCase
AF:
0.331
EpiControl
AF:
0.340

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.059
BayesDel_addAF
Benign
-1.0
T
BayesDel_noAF
Benign
-1.1
CADD
Benign
0.81
DANN
Benign
0.63
DEOGEN2
Benign
0.0038
T
FATHMM_MKL
Benign
0.000030
N
LIST_S2
Benign
0.19
T
MetaRNN
Benign
0.0000011
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.0
N
PrimateAI
Benign
0.35
T
PROVEAN
Benign
1.8
N
REVEL
Benign
0.19
Sift
Benign
1.0
T
Sift4G
Benign
1.0
T
Polyphen
0.0
B
Vest4
0.011
MPC
0.094
ClinPred
0.0017
T
GERP RS
0.79
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.17
gMVP
0.0099

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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.

Other links and lift over

dbSNP: rs4830842; hg19: chrX-13337059; COSMIC: COSV66075703; COSMIC: COSV66075703; API