12-74538330-C-A
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Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_001136262.2(ATXN7L3B):c.218C>A(p.Pro73Gln) variant causes a missense change. The variant allele was found at a frequency of 0.00000571 in 1,400,314 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: not found (cov: 33)
Exomes 𝑓: 0.0000057 ( 0 hom. )
Consequence
ATXN7L3B
NM_001136262.2 missense
NM_001136262.2 missense
Scores
2
6
10
Clinical Significance
Conservation
PhyloP100: 3.58
Genes affected
ATXN7L3B (HGNC:37931): (ataxin 7 like 3B) Involved in regulation of gene expression. Located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]
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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=0.30110043).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ATXN7L3B | NM_001136262.2 | c.218C>A | p.Pro73Gln | missense_variant | 1/1 | ENST00000519948.4 | NP_001129734.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
ATXN7L3B | ENST00000519948.4 | c.218C>A | p.Pro73Gln | missense_variant | 1/1 | 6 | NM_001136262.2 | ENSP00000430000.2 | ||
ENSG00000257386 | ENST00000550926.1 | n.190G>T | non_coding_transcript_exon_variant | 2/2 | 3 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 genomes
Cov.:
33
GnomAD3 exomes AF: 0.00000643 AC: 1AN: 155504Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 82360
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GnomAD4 exome AF: 0.00000571 AC: 8AN: 1400314Hom.: 0 Cov.: 30 AF XY: 0.00000724 AC XY: 5AN XY: 690726
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GnomAD4 genome Cov.: 33
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33
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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 07, 2023 | The c.218C>A (p.P73Q) alteration is located in exon 1 (coding exon 1) of the ATXN7L3B gene. This alteration results from a C to A substitution at nucleotide position 218, causing the proline (P) at amino acid position 73 to be replaced by a glutamine (Q). 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
Uncertain
D
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
DEOGEN2
Benign
T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T
M_CAP
Benign
D
MetaRNN
Benign
T
MetaSVM
Benign
T
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D
REVEL
Benign
Sift
Pathogenic
D
Sift4G
Benign
T
Polyphen
D
Vest4
MutPred
Gain of sheet (P = 0.0085);
MVP
MPC
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at