Genetic Variant PHACTR3:p.Gly6Arg (chr20-59577524-G-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001199505.1(PHACTR3):c.16G>A(p.Gly6Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000067 in 149,352 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/17 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G6W) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0000067 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

PHACTR3
NM_001199505.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.04

Publications

0 publications found

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.06348279).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001199505.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PHACTR3	NM_001199505.1		c.16G>A	p.Gly6Arg	missense	Exon 1 of 13	NP_001186434.1	Q96KR7-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PHACTR3	ENST00000359926.7	TSL:2	c.16G>A	p.Gly6Arg	missense	Exon 1 of 13	ENSP00000353002.3	Q96KR7-4
	PHACTR3	ENST00000944653.1		c.-376G>A		5_prime_UTR	Exon 1 of 11	ENSP00000614712.1

Frequencies

GnomAD3 genomes

AF:

0.00000670

AC:

AN:

149352

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000666

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

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

999838

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

470792

African (AFR)

AF:

0.00

AC:

AN:

20052

American (AMR)

AF:

0.00

AC:

AN:

5660

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

10852

East Asian (EAS)

AF:

0.00

AC:

AN:

18962

South Asian (SAS)

AF:

0.00

AC:

AN:

18826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

16488

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2456

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

868768

Other (OTH)

AF:

0.00

AC:

AN:

37774

GnomAD4 genome

AF:

0.00000670

AC:

AN:

149352

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

72810

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41146

American (AMR)

AF:

0.0000666

AC:

AN:

15018

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3440

East Asian (EAS)

AF:

0.00

AC:

AN:

5154

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9472

Middle Eastern (MID)

AF:

0.00

AC:

AN:

312

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67012

Other (OTH)

AF:

0.00

AC:

AN:

2058

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.30

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.71

CADD

Benign

(source)

DANN

Uncertain

0.98

Eigen

Benign

-0.87

Eigen_PC

Benign

-0.76

FATHMM_MKL

Benign

0.26

LIST_S2

Benign

0.36

M_CAP

Benign

0.082

MetaRNN

Benign

0.063

MetaSVM

Benign

-1.0

PhyloP100

1.0

PROVEAN

Benign

1.1

REVEL

Benign

0.054

Sift

Benign

0.32

Sift4G

Benign

0.92

Vest4

0.23

MutPred

0.35

Gain of methylation at G6 (P = 5e-04)

MVP

0.068

ClinPred

0.088

GERP RS

1.5

PromoterAI

0.0096

Neutral

(source)

Mutation Taster

=97/3

polymorphism

(source)

Splicing

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over