16-28823371-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_007245.4(ATXN2L):​c.112C>T​(p.Leu38Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000132 in 152,020 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

ATXN2L
NM_007245.4 missense

Scores

1
7
11

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.04
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 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.2073276).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ATXN2LNM_007245.4 linkc.112C>T p.Leu38Phe 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.112C>T p.Leu38Phe missense_variant Exon 1 of 22 1 NM_007245.4 ENSP00000338718.4 Q8WWM7-1

Frequencies

GnomAD3 genomes
AF:
0.0000132
AC:
2
AN:
152020
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000483
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
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
0.00
AC:
0
AN:
1192978
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
579830
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:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000132
AC:
2
AN:
152020
Hom.:
0
Cov.:
32
AF XY:
0.0000135
AC XY:
1
AN XY:
74260
show subpopulations
Gnomad4 AFR
AF:
0.0000483
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:
0.00000378

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Feb 05, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.112C>T (p.L38F) 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 112, causing the leucine (L) at amino acid position 38 to be replaced by a phenylalanine (F). 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
0.071
BayesDel_addAF
Benign
-0.13
T
BayesDel_noAF
Benign
-0.42
CADD
Uncertain
24
DANN
Uncertain
1.0
DEOGEN2
Benign
0.026
.;.;.;T;.;T;.
Eigen
Uncertain
0.36
Eigen_PC
Uncertain
0.36
FATHMM_MKL
Uncertain
0.77
D
LIST_S2
Benign
0.78
T;T;T;T;T;T;T
M_CAP
Uncertain
0.25
D
MetaRNN
Benign
0.21
T;T;T;T;T;T;T
MetaSVM
Benign
-0.92
T
MutationAssessor
Benign
0.55
N;N;N;N;N;.;N
PrimateAI
Pathogenic
0.91
D
PROVEAN
Benign
-0.13
N;N;N;N;N;N;N
REVEL
Benign
0.079
Sift
Uncertain
0.0050
D;D;D;D;D;D;D
Sift4G
Uncertain
0.057
T;T;T;T;T;T;T
Polyphen
0.99
D;D;D;D;.;.;.
Vest4
0.088
MutPred
0.13
Loss of glycosylation at P41 (P = 0.2269);Loss of glycosylation at P41 (P = 0.2269);Loss of glycosylation at P41 (P = 0.2269);Loss of glycosylation at P41 (P = 0.2269);Loss of glycosylation at P41 (P = 0.2269);Loss of glycosylation at P41 (P = 0.2269);Loss of glycosylation at P41 (P = 0.2269);
MVP
0.26
MPC
0.54
ClinPred
0.63
D
GERP RS
4.0
Varity_R
0.23
gMVP
0.13

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: rs1396513310; hg19: chr16-28834692; API