chr20-59767354-C-T
Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2
The NM_080672.5(PHACTR3):c.710C>T(p.Pro237Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000931 in 1,614,092 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.00072 ( 0 hom., cov: 34)
Exomes 𝑓: 0.00095 ( 2 hom. )
Consequence
PHACTR3
NM_080672.5 missense
NM_080672.5 missense
Scores
4
13
Clinical Significance
Conservation
PhyloP100: 3.54
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 Benign. Variant got -8 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.030415177).
BS2
?
High AC in GnomAd at 110 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PHACTR3 | NM_080672.5 | c.710C>T | p.Pro237Leu | missense_variant | 5/13 | ENST00000371015.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PHACTR3 | ENST00000371015.6 | c.710C>T | p.Pro237Leu | missense_variant | 5/13 | 1 | NM_080672.5 | A1 |
Frequencies
GnomAD3 genomes ? AF: 0.000723 AC: 110AN: 152232Hom.: 0 Cov.: 34
GnomAD3 genomes
?
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34
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GnomAD3 exomes AF: 0.000560 AC: 140AN: 250064Hom.: 0 AF XY: 0.000583 AC XY: 79AN XY: 135500
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GnomAD4 exome AF: 0.000954 AC: 1394AN: 1461742Hom.: 2 Cov.: 32 AF XY: 0.000945 AC XY: 687AN XY: 727174
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GnomAD4 genome ? AF: 0.000715 AC: 109AN: 152350Hom.: 0 Cov.: 34 AF XY: 0.000685 AC XY: 51AN XY: 74500
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ESP6500AA
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74
Asia WGS
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3478
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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 | Aug 02, 2021 | The c.710C>T (p.P237L) alteration is located in exon 5 (coding exon 5) of the PHACTR3 gene. This alteration results from a C to T substitution at nucleotide position 710, causing the proline (P) at amino acid position 237 to be replaced by a leucine (L). 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
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;D;.;.
M_CAP
Benign
T
MetaRNN
Benign
T;T;T;T;T
MetaSVM
Benign
T
MutationTaster
Benign
D;D;D;D;D;D;D
PrimateAI
Benign
T
PROVEAN
Benign
N;N;N;N;N
REVEL
Benign
Sift
Benign
T;D;D;D;D
Sift4G
Uncertain
D;D;D;D;D
Polyphen
0.63
.;P;.;.;.
Vest4
MVP
MPC
0.41
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