rs142953622

Variant summary

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

The NM_007245.4(ATXN2L):​c.493C>G​(p.Arg165Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,842 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R165W) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)
Exomes š‘“: 6.8e-7 ( 0 hom. )

Consequence

ATXN2L
NM_007245.4 missense

Scores

1
7
11

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.23
Variant links:
Genes affected
ATXN2L (HGNC:31326): (ataxin 2 like) This gene encodes an ataxin type 2 related protein of unknown function. This protein is a member of the spinocerebellar ataxia (SCAs) family, which is associated with a complex group of neurodegenerative disorders. Several alternatively spliced transcripts encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

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=0.28776467).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ATXN2LNM_007245.4 linkc.493C>G p.Arg165Gly missense_variant Exon 5 of 22 ENST00000336783.9 NP_009176.2 Q8WWM7-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ATXN2LENST00000336783.9 linkc.493C>G p.Arg165Gly missense_variant Exon 5 of 22 1 NM_007245.4 ENSP00000338718.4 Q8WWM7-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000398
AC:
1
AN:
251474
Hom.:
0
AF XY:
0.00000736
AC XY:
1
AN XY:
135914
show subpopulations
Gnomad AFR exome
AF:
0.00
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:
0.00000879
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461842
Hom.:
0
Cov.:
32
AF XY:
0.00000138
AC XY:
1
AN XY:
727220
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:
8.99e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
ExAC
AF:
0.00000824
AC:
1
EpiCase
AF:
0.00
EpiControl
AF:
0.0000593

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.73
BayesDel_addAF
Benign
-0.041
T
BayesDel_noAF
Benign
-0.30
CADD
Benign
23
DANN
Uncertain
1.0
DEOGEN2
Benign
0.32
.;.;.;T;.;T;.;.;.
Eigen
Benign
0.15
Eigen_PC
Benign
0.16
FATHMM_MKL
Uncertain
0.87
D
LIST_S2
Uncertain
0.88
D;D;D;D;D;D;D;D;D
M_CAP
Benign
0.026
D
MetaRNN
Benign
0.29
T;T;T;T;T;T;T;T;T
MetaSVM
Benign
-0.82
T
MutationAssessor
Benign
1.5
L;L;L;L;L;.;L;.;.
PrimateAI
Uncertain
0.67
T
PROVEAN
Uncertain
-3.6
D;D;D;D;D;D;D;D;D
REVEL
Benign
0.12
Sift
Uncertain
0.023
D;D;D;D;D;D;D;D;D
Sift4G
Uncertain
0.0090
D;D;D;D;D;D;D;D;D
Polyphen
0.89
P;P;D;P;.;.;.;.;.
Vest4
0.68
MutPred
0.38
Gain of loop (P = 0.0312);Gain of loop (P = 0.0312);Gain of loop (P = 0.0312);Gain of loop (P = 0.0312);Gain of loop (P = 0.0312);Gain of loop (P = 0.0312);Gain of loop (P = 0.0312);.;.;
MVP
0.45
MPC
1.2
ClinPred
0.95
D
GERP RS
2.3
Varity_R
0.47
gMVP
0.89

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.

Other links and lift over

dbSNP: rs142953622; hg19: chr16-28837588; API