3-53877688-T-C
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_022899.5(ACTR8):c.469A>G(p.Thr157Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000062 in 1,614,040 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000053 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000063 ( 0 hom. )
Consequence
ACTR8
NM_022899.5 missense
NM_022899.5 missense
Scores
6
8
5
Clinical Significance
Conservation
PhyloP100: 7.55
Genes affected
ACTR8 (HGNC:14672): (actin related protein 8) Predicted to enable ATP binding activity. Predicted to be involved in chromatin remodeling; double-strand break repair; and regulation of transcription, DNA-templated. Located in centrosome and nucleoplasm. Part of Ino80 complex. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ACTR8 | NM_022899.5 | c.469A>G | p.Thr157Ala | missense_variant | 4/13 | ENST00000335754.8 | |
ACTR8 | NM_001410774.1 | c.136A>G | p.Thr46Ala | missense_variant | 4/13 | ||
ACTR8 | XM_005265587.6 | c.469A>G | p.Thr157Ala | missense_variant | 4/14 | ||
ACTR8 | XM_047449239.1 | c.469A>G | p.Thr157Ala | missense_variant | 4/9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ACTR8 | ENST00000335754.8 | c.469A>G | p.Thr157Ala | missense_variant | 4/13 | 2 | NM_022899.5 | P1 | |
ACTR8 | ENST00000482349.5 | c.136A>G | p.Thr46Ala | missense_variant | 4/13 | 2 | |||
ACTR8 | ENST00000498740.1 | c.136A>G | p.Thr46Ala | missense_variant | 4/5 | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.0000526 AC: 8AN: 152222Hom.: 0 Cov.: 33
GnomAD3 genomes
?
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GnomAD3 exomes AF: 0.0000318 AC: 8AN: 251418Hom.: 0 AF XY: 0.0000442 AC XY: 6AN XY: 135888
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GnomAD4 exome AF: 0.0000629 AC: 92AN: 1461818Hom.: 0 Cov.: 30 AF XY: 0.0000578 AC XY: 42AN XY: 727202
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GnomAD4 genome ? AF: 0.0000526 AC: 8AN: 152222Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74374
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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 | Sep 14, 2023 | The c.469A>G (p.T157A) alteration is located in exon 4 (coding exon 4) of the ACTR8 gene. This alteration results from a A to G substitution at nucleotide position 469, causing the threonine (T) at amino acid position 157 to be replaced by an alanine (A). 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
Pathogenic
D
BayesDel_noAF
Pathogenic
Cadd
Uncertain
Dann
Uncertain
DEOGEN2
Uncertain
T;.;T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D;D
M_CAP
Uncertain
D
MetaRNN
Uncertain
D;D;D
MetaSVM
Pathogenic
D
MutationAssessor
Pathogenic
M;.;.
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N;D
REVEL
Pathogenic
Sift
Benign
T;T;T
Sift4G
Benign
T;T;D
Polyphen
P;.;.
Vest4
MVP
MPC
ClinPred
T
GERP RS
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