chr6-13272864-C-A
Variant summary
Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2PP2PP5_Moderate
The NM_030948.6(PHACTR1):c.1396C>A(p.Leu466Met) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (★).
Frequency
Genomes: not found (cov: 33)
Consequence
PHACTR1
NM_030948.6 missense
NM_030948.6 missense
Scores
4
10
4
Clinical Significance
Conservation
PhyloP100: 4.75
Genes affected
PHACTR1 (HGNC:20990): (phosphatase and actin regulator 1) The protein encoded by this gene is a member of the phosphatase and actin regulator family of proteins. This family member can bind actin and regulate the reorganization of the actin cytoskeleton. It plays a role in tubule formation and in endothelial cell survival. Polymorphisms in this gene are associated with susceptibility to myocardial infarction, coronary artery disease and cervical artery dissection. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Apr 2016]
TBC1D7 (HGNC:21066): (TBC1 domain family member 7) This gene encodes a member of the TBC-domain containing protein family. The encoded protein functions as a subunit of the tuberous sclerosis TSC1-TSC2 complex which plays a role in the regulation of cellular growth and differentiation. Mutations in this gene have been associated with autosomal recessive megalencephaly. Alternative splicing results in multiple transcript variants. Naturally occurring readthrough transcription occurs between this locus and downstream LOC100130357. [provided by RefSeq, Jan 2016]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 5 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PP2
?
Missense variant where missense usually causes diseases, PHACTR1
PP5
?
Variant 6-13272864-C-A is Pathogenic according to our data. Variant chr6-13272864-C-A is described in ClinVar as [Pathogenic]. Clinvar id is 1679588.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PHACTR1 | NM_030948.6 | c.1396C>A | p.Leu466Met | missense_variant | 11/15 | ENST00000332995.12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PHACTR1 | ENST00000332995.12 | c.1396C>A | p.Leu466Met | missense_variant | 11/15 | 2 | NM_030948.6 | P3 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 genomes
?
Cov.:
33
GnomAD4 exome Cov.: 30
GnomAD4 exome
Cov.:
30
GnomAD4 genome ? Cov.: 33
GnomAD4 genome
?
Cov.:
33
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Developmental and epileptic encephalopathy, 70 Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | New York Genome Center | May 18, 2021 | The mosaic de novo c.1606C>A, p.Leu536Met missense variant identified in PHACTR1 has not been reported in the literature. This variant is not reported in thegnomAD v3.1 database, indicating a rare allele, and in silico tools predict a deleterious effect. The variant is located in the RPEL repeat domain 3 (RPEL3). Many of the pathogenic variants in PHACTR1 have been identified within one of the RPEL domains (PMID: 30256902; PMID: 23033978; PMID:28135719). RPEL repeats have been shown to be required for unpolymerised actin binding and proteins containing RPEL repeats are able to modify cell shape and/or are important in the regulation of geneexpression by the actin cytoskeleton. RPEL repeats can be found in association with the SAP motif, which could be involved in DNA binding (PMID:12732141; PMID:15620697). Based on the available evidence, the variant c.1606C>A, p.Leu536Met in the PHACTR1 gene is classified as pathogenic. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Uncertain
Cadd
Pathogenic
Dann
Uncertain
DEOGEN2
Benign
T;.;T;T
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Uncertain
D
M_CAP
Benign
D
MetaRNN
Uncertain
D;D;D;D
MetaSVM
Uncertain
T
MutationAssessor
Uncertain
M;M;.;.
MutationTaster
Benign
N;N;N
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N;N;N
REVEL
Uncertain
Sift
Uncertain
D;D;D;D
Sift4G
Uncertain
D;D;D;D
Polyphen
D;D;.;.
Vest4
MutPred
Gain of methylation at K461 (P = 0.0748);Gain of methylation at K461 (P = 0.0748);.;.;
MVP
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
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
Publications
No publications associated with this variant yet.