chr1-109490097-A-G
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_001350175.2(ATXN7L2):c.1301A>G(p.His434Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000156 in 1,589,156 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000053 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00017 ( 1 hom. )
Consequence
ATXN7L2
NM_001350175.2 missense
NM_001350175.2 missense
Scores
4
5
10
Clinical Significance
Conservation
PhyloP100: 4.62
Genes affected
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 3 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.748
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ATXN7L2 | NM_001350175.2 | c.1301A>G | p.His434Arg | missense_variant | 8/11 | ENST00000683729.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ATXN7L2 | ENST00000683729.1 | c.1301A>G | p.His434Arg | missense_variant | 8/11 | NM_001350175.2 | P2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000526 AC: 8AN: 152084Hom.: 0 Cov.: 32
GnomAD3 genomes
?
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GnomAD3 exomes AF: 0.0000265 AC: 6AN: 226532Hom.: 0 AF XY: 0.0000164 AC XY: 2AN XY: 121982
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GnomAD4 exome AF: 0.000167 AC: 240AN: 1437072Hom.: 1 Cov.: 31 AF XY: 0.000181 AC XY: 129AN XY: 712740
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GnomAD4 genome ? AF: 0.0000526 AC: 8AN: 152084Hom.: 0 Cov.: 32 AF XY: 0.0000673 AC XY: 5AN XY: 74294
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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 15, 2021 | The c.1205A>G (p.H402R) alteration is located in exon 8 (coding exon 8) of the ATXN7L2 gene. This alteration results from a A to G substitution at nucleotide position 1205, causing the histidine (H) at amino acid position 402 to be replaced by an arginine (R). 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
Uncertain
DEOGEN2
Benign
T
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T
M_CAP
Benign
T
MetaRNN
Pathogenic
D
MetaSVM
Benign
T
MutationAssessor
Uncertain
M
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D
REVEL
Benign
Sift
Uncertain
D
Sift4G
Benign
T
Polyphen
D
Vest4
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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Calibrated prediction
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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