Variant 1-28459169-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001048183.3(PHACTR4):c.101A>G(p.Lys34Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000013 in 1,461,768 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: not found (cov: 31)

Exomes 𝑓: 0.000013 ( 0 hom. )

Consequence

PHACTR4
NM_001048183.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.95

Variant links:

Genes affected

PHACTR4 (HGNC:25793): (phosphatase and actin regulator 4) This gene encodes a member of the phosphatase and actin regulator (PHACTR) family. Other PHACTR family members have been shown to inhibit protein phosphatase 1 (PP1) activity, and the homolog of this gene in the mouse has been shown to interact with actin and PP1. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

PHACTR4 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.21873772).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PHACTR4	NM_001048183.3 linkuse as main transcript	c.101A>G	p.Lys34Arg	missense_variant	3/14	ENST00000373839.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PHACTR4	ENST00000373839.8 linkuse as main transcript	c.101A>G	p.Lys34Arg	missense_variant	3/14	1	NM_001048183.3	P2	Q8IZ21-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000321

AC:

AN:

249432

Hom.:

AF XY:

0.0000296

AC XY:

AN XY:

135330

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000261

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000130

AC:

AN:

1461768

Hom.:

Cov.:

AF XY:

0.0000220

AC XY:

AN XY:

727190

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:

0.000209

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000579

AC:

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 17, 2022

The c.131A>G (p.K44R) alteration is located in exon 2 (coding exon 2) of the PHACTR4 gene. This alteration results from a A to G substitution at nucleotide position 131, causing the lysine (K) at amino acid position 44 to be replaced by an arginine (R). 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

Benign

0.11

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.28

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.20

T;.;T;.

Eigen

Uncertain

0.66

Eigen_PC

Uncertain

0.66

FATHMM_MKL

Uncertain

0.92

LIST_S2

Benign

0.86

D;D;T;D

M_CAP

Benign

0.018

MetaRNN

Benign

0.22

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.5

L;.;.;.

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.69

PROVEAN

Benign

-2.3

N;.;.;N

REVEL

Benign

0.19

Sift

Benign

0.18

T;.;.;T

Sift4G

Benign

0.061

T;T;T;T

Polyphen

1.0

D;.;.;D

Vest4

0.62

MutPred

0.11

Loss of methylation at K34 (P = 0.0168);.;.;.;

MVP

0.62

MPC

0.40

ClinPred

0.47

GERP RS

5.3

Varity_R

0.24

gMVP

0.12

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