Genetic Variant PHACTR3:p.Arg16Leu (chr20-59605061-G-T) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_080672.5(PHACTR3):c.47G>T(p.Arg16Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000356 in 1,402,944 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 31)

Exomes 𝑓: 8.0e-7 ( 0 hom. )

Consequence

PHACTR3
NM_080672.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.40

Variant links:

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]

PHACTR3 links:

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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 rank	MANE	Protein	UniProt
PHACTR3	NM_080672.5 link	c.47G>T	p.Arg16Leu	missense_variant	Exon 1 of 13	ENST00000371015.6	NP_542403.1	Q96KR7-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
PHACTR3	ENST00000371015.6 link	c.47G>T	p.Arg16Leu	missense_variant	Exon 1 of 13	1	NM_080672.5	ENSP00000360054.1	Q96KR7-1
PHACTR3	ENST00000434923.1 link	c.47G>T	p.Arg16Leu	missense_variant	Exon 3 of 4	5		ENSP00000390915.1	F6RP66
PHACTR3	ENST00000359926.7 link	c.109+27444G>T		intron_variant	Intron 1 of 12	2		ENSP00000353002.3	Q96KR7-4

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

151910

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

7.99e-7

AC:

AN:

1251034

Hom.:

Cov.:

AF XY:

0.00000164

AC XY:

AN XY:

610970

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.96e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000263

AC:

AN:

151910

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74192

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000262

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000453

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Dec 25, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.47G>T (p.R16L) alteration is located in exon 1 (coding exon 1) of the PHACTR3 gene. This alteration results from a G to T substitution at nucleotide position 47, causing the arginine (R) at amino acid position 16 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.76

BayesDel_addAF

Uncertain

0.026

BayesDel_noAF

Benign

-0.20

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.035

.;T

Eigen

Uncertain

0.58

Eigen_PC

Uncertain

0.53

FATHMM_MKL

Uncertain

0.88

LIST_S2

Benign

0.71

T;D

M_CAP

Pathogenic

0.68

MetaRNN

Uncertain

0.46

T;T

MetaSVM

Benign

-0.81

PrimateAI

Pathogenic

0.86

PROVEAN

Pathogenic

-7.0

D;D

REVEL

Benign

0.18

Sift

Pathogenic

0.0

D;D

Sift4G

Pathogenic

0.0

D;D

Polyphen

0.99

.;D

Vest4

0.53

MutPred

0.24

Gain of glycosylation at S19 (P = 0.0876);Gain of glycosylation at S19 (P = 0.0876);

MVP

0.41

MPC

0.17

ClinPred

0.99

GERP RS

4.3

Varity_R

0.35

gMVP

0.57

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over