7-105614608-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_020725.2(ATXN7L1):​c.1726G>A​(p.Ala576Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000529 in 1,551,446 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000099 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000048 ( 0 hom. )

Consequence

ATXN7L1
NM_020725.2 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.25
Variant links:
Genes affected
ATXN7L1 (HGNC:22210): (ataxin 7 like 1)

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.059191108).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ATXN7L1NM_020725.2 linkc.1726G>A p.Ala576Thr missense_variant Exon 10 of 12 ENST00000419735.8 NP_065776.1 Q9ULK2-1
ATXN7L1NM_001385596.1 linkc.1726G>A p.Ala576Thr missense_variant Exon 10 of 12 NP_001372525.1
ATXN7L1NM_138495.2 linkc.1354G>A p.Ala452Thr missense_variant Exon 8 of 10 NP_612504.1 Q9ULK2-3
ATXN7L1NM_001318229.2 linkc.1078G>A p.Ala360Thr missense_variant Exon 10 of 10 NP_001305158.1 Q9BTQ8

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ATXN7L1ENST00000419735.8 linkc.1726G>A p.Ala576Thr missense_variant Exon 10 of 12 1 NM_020725.2 ENSP00000410759.3 Q9ULK2-1

Frequencies

GnomAD3 genomes
AF:
0.0000987
AC:
15
AN:
151938
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000314
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000416
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000765
AC:
12
AN:
156954
Hom.:
0
AF XY:
0.000108
AC XY:
9
AN XY:
83066
show subpopulations
Gnomad AFR exome
AF:
0.000125
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000396
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000164
Gnomad OTH exome
AF:
0.000226
GnomAD4 exome
AF:
0.0000479
AC:
67
AN:
1399508
Hom.:
0
Cov.:
32
AF XY:
0.0000608
AC XY:
42
AN XY:
690266
show subpopulations
Gnomad4 AFR exome
AF:
0.000411
Gnomad4 AMR exome
AF:
0.0000280
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000518
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000834
Gnomad4 OTH exome
AF:
0.0000517
GnomAD4 genome
AF:
0.0000987
AC:
15
AN:
151938
Hom.:
0
Cov.:
32
AF XY:
0.000108
AC XY:
8
AN XY:
74176
show subpopulations
Gnomad4 AFR
AF:
0.000314
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000416
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000197
Hom.:
0
Bravo
AF:
0.0000945
ESP6500AA
AF:
0.000723
AC:
1
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.000184
AC:
5

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Jan 21, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1726G>A (p.A576T) alteration is located in exon 10 (coding exon 10) of the ATXN7L1 gene. This alteration results from a G to A substitution at nucleotide position 1726, causing the alanine (A) at amino acid position 576 to be replaced by a threonine (T). 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
0.063
BayesDel_addAF
Benign
-0.49
T
BayesDel_noAF
Benign
-0.62
CADD
Benign
21
DANN
Uncertain
0.98
DEOGEN2
Benign
0.0068
T;.;T;T
Eigen
Benign
-0.14
Eigen_PC
Benign
0.082
FATHMM_MKL
Benign
0.56
D
LIST_S2
Benign
0.73
T;T;T;T
M_CAP
Benign
0.0022
T
MetaRNN
Benign
0.059
T;T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.0
L;.;.;.
PrimateAI
Benign
0.30
T
PROVEAN
Benign
-0.29
N;N;N;N
REVEL
Benign
0.038
Sift
Benign
0.20
T;T;D;T
Sift4G
Benign
0.25
T;T;T;T
Polyphen
0.031
B;B;.;.
Vest4
0.10
MVP
0.53
MPC
0.41
ClinPred
0.049
T
GERP RS
4.7
Varity_R
0.045
gMVP
0.22

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: rs376781439; hg19: chr7-105255055; COSMIC: COSV66300629; API