17-44197234-T-C
Position:
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The NM_001382309.1(ATXN7L3):āc.350A>Gā(p.Asn117Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000333 in 1,591,722 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: š 0.000020 ( 0 hom., cov: 32)
Exomes š: 0.000035 ( 0 hom. )
Consequence
ATXN7L3
NM_001382309.1 missense
NM_001382309.1 missense
Scores
1
2
16
Clinical Significance
Conservation
PhyloP100: 7.02
Genes affected
ATXN7L3 (HGNC:25416): (ataxin 7 like 3) Enables nuclear receptor coactivator activity. Involved in histone deubiquitination; histone monoubiquitination; and positive regulation of transcription, DNA-templated. Located in nucleus. Part of DUBm complex and SAGA complex. [provided by Alliance of Genome Resources, Apr 2022]
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=0.11008033).
BS2
High AC in GnomAdExome4 at 50 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ATXN7L3 | NM_001382309.1 | c.350A>G | p.Asn117Ser | missense_variant | 4/13 | ENST00000587097.6 | NP_001369238.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
ATXN7L3 | ENST00000587097.6 | c.350A>G | p.Asn117Ser | missense_variant | 4/13 | 5 | NM_001382309.1 | ENSP00000465614.2 |
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152120Hom.: 0 Cov.: 32
GnomAD3 genomes
AF:
AC:
3
AN:
152120
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.0000647 AC: 15AN: 231770Hom.: 0 AF XY: 0.0000880 AC XY: 11AN XY: 125052
GnomAD3 exomes
AF:
AC:
15
AN:
231770
Hom.:
AF XY:
AC XY:
11
AN XY:
125052
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.0000347 AC: 50AN: 1439602Hom.: 0 Cov.: 32 AF XY: 0.0000392 AC XY: 28AN XY: 713472
GnomAD4 exome
AF:
AC:
50
AN:
1439602
Hom.:
Cov.:
32
AF XY:
AC XY:
28
AN XY:
713472
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome AF: 0.0000197 AC: 3AN: 152120Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74324
GnomAD4 genome
AF:
AC:
3
AN:
152120
Hom.:
Cov.:
32
AF XY:
AC XY:
1
AN XY:
74324
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Bravo
AF:
ExAC
AF:
AC:
6
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Nov 18, 2022 | The c.350A>G (p.N117S) alteration is located in exon 3 (coding exon 3) of the ATXN7L3 gene. This alteration results from a A to G substitution at nucleotide position 350, causing the asparagine (N) at amino acid position 117 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
DEOGEN2
Benign
.;T;T;T;T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D;D;D;D
M_CAP
Benign
T
MetaRNN
Benign
T;T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
L;L;.;.;.
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N;.;.;.
REVEL
Benign
Sift
Benign
T;T;.;.;.
Sift4G
Benign
T;T;T;.;.
Polyphen
D;B;.;.;.
Vest4
MutPred
Gain of phosphorylation at N117 (P = 0.0048);Gain of phosphorylation at N117 (P = 0.0048);Gain of phosphorylation at N117 (P = 0.0048);Gain of phosphorylation at N117 (P = 0.0048);Gain of phosphorylation at N117 (P = 0.0048);
MVP
MPC
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at