16-28823494-C-T

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_007245.4(ATXN2L):​c.235C>T​(p.Pro79Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000318 in 1,382,168 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00018 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000014 ( 0 hom. )

Consequence

ATXN2L
NM_007245.4 missense

Scores

1
2
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.610
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 Likely_benign. Variant got -6 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.08371219).
BS2
High AC in GnomAd4 at 27 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ATXN2LNM_007245.4 linkc.235C>T p.Pro79Ser missense_variant Exon 1 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.235C>T p.Pro79Ser missense_variant Exon 1 of 22 1 NM_007245.4 ENSP00000338718.4 Q8WWM7-1

Frequencies

GnomAD3 genomes
AF:
0.000177
AC:
27
AN:
152120
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000628
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:
0.000478
GnomAD4 exome
AF:
0.0000138
AC:
17
AN:
1229940
Hom.:
0
Cov.:
32
AF XY:
0.00000997
AC XY:
6
AN XY:
601912
show subpopulations
Gnomad4 AFR exome
AF:
0.000651
Gnomad4 AMR exome
AF:
0.0000654
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:
0.000177
AC:
27
AN:
152228
Hom.:
0
Cov.:
32
AF XY:
0.000161
AC XY:
12
AN XY:
74426
show subpopulations
Gnomad4 AFR
AF:
0.000626
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:
0.000473
Alfa
AF:
0.0000712
Hom.:
0
Bravo
AF:
0.000227

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Dec 03, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.235C>T (p.P79S) alteration is located in exon 1 (coding exon 1) of the ATXN2L gene. This alteration results from a C to T substitution at nucleotide position 235, causing the proline (P) at amino acid position 79 to be replaced by a serine (S). 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
0.062
BayesDel_addAF
Benign
-0.55
T
BayesDel_noAF
Benign
-0.65
CADD
Benign
21
DANN
Benign
0.97
DEOGEN2
Benign
0.029
.;.;.;T;.;T;.
Eigen
Benign
-0.68
Eigen_PC
Benign
-0.54
FATHMM_MKL
Uncertain
0.83
D
LIST_S2
Benign
0.80
T;T;T;T;T;T;T
M_CAP
Uncertain
0.22
D
MetaRNN
Benign
0.084
T;T;T;T;T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.34
N;N;N;N;N;.;N
PrimateAI
Pathogenic
0.85
D
PROVEAN
Benign
-0.020
N;N;N;N;N;N;N
REVEL
Benign
0.027
Sift
Benign
0.13
T;T;T;T;T;T;T
Sift4G
Benign
0.69
T;T;T;T;T;T;T
Polyphen
0.31
B;B;B;B;.;.;.
Vest4
0.20
MutPred
0.13
Gain of glycosylation at P79 (P = 0.0324);Gain of glycosylation at P79 (P = 0.0324);Gain of glycosylation at P79 (P = 0.0324);Gain of glycosylation at P79 (P = 0.0324);Gain of glycosylation at P79 (P = 0.0324);Gain of glycosylation at P79 (P = 0.0324);Gain of glycosylation at P79 (P = 0.0324);
MVP
0.24
MPC
0.52
ClinPred
0.12
T
GERP RS
1.8
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.031
gMVP
0.18

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: rs1004412705; hg19: chr16-28834815; API