20-59773401-C-A
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The NM_080672.5(PHACTR3):c.874C>A(p.Arg292Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000112 in 1,614,020 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: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000012 ( 0 hom. )
Consequence
PHACTR3
NM_080672.5 missense
NM_080672.5 missense
Scores
6
11
Clinical Significance
Conservation
PhyloP100: 2.96
Genes affected
PHACTR3 (HGNC:15833): (phosphatase and actin regulator 3) This gene encodes a member of the phosphatase and actin regulator protein family. The encoded protein is associated with the nuclear scaffold in proliferating cells, and binds to actin and the catalytic subunit of protein phosphatase-1, suggesting that it functions as a regulatory subunit of protein phosphatase-1. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2013]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -6 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.11283541).
BS2
?
High AC in GnomAdExome at 17 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PHACTR3 | NM_080672.5 | c.874C>A | p.Arg292Ser | missense_variant | 6/13 | ENST00000371015.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PHACTR3 | ENST00000371015.6 | c.874C>A | p.Arg292Ser | missense_variant | 6/13 | 1 | NM_080672.5 | A1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152214Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000678 AC: 17AN: 250642Hom.: 0 AF XY: 0.0000369 AC XY: 5AN XY: 135498
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GnomAD4 exome AF: 0.0000116 AC: 17AN: 1461806Hom.: 0 Cov.: 31 AF XY: 0.00000825 AC XY: 6AN XY: 727206
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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 | May 18, 2023 | The c.874C>A (p.R292S) alteration is located in exon 6 (coding exon 6) of the PHACTR3 gene. This alteration results from a C to A substitution at nucleotide position 874, causing the arginine (R) at amino acid position 292 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
Uncertain
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Uncertain
Dann
Uncertain
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Benign
D
LIST_S2
Uncertain
D;D;D;.;.;D
M_CAP
Benign
T
MetaRNN
Benign
T;T;T;T;T;T
MetaSVM
Benign
T
MutationTaster
Benign
D;D;D;D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N;N;N;N;N
REVEL
Benign
Sift
Benign
T;D;D;D;D;T
Sift4G
Benign
T;T;T;T;T;T
Polyphen
1.0, 0.98
.;D;.;.;.;D
Vest4
MutPred
0.21
.;Gain of phosphorylation at R292 (P = 0.0385);.;.;.;.;
MVP
MPC
0.33
ClinPred
T
GERP RS
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