Variant 20-59605096-T-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_080672.5(PHACTR3):c.82T>G(p.Ser28Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000814 in 1,228,180 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 8.1e-7 ( 0 hom. )

Consequence

PHACTR3
NM_080672.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.42

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 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.09871897).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PHACTR3	NM_080672.5 linkuse as main transcript	c.82T>G	p.Ser28Ala	missense_variant	1/13	ENST00000371015.6	NP_542403.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PHACTR3	ENST00000371015.6 linkuse as main transcript	c.82T>G	p.Ser28Ala	missense_variant	1/13	1	NM_080672.5	ENSP00000360054	A1	Q96KR7-1
PHACTR3	ENST00000434923.1 linkuse as main transcript	c.82T>G	p.Ser28Ala	missense_variant	3/4	5		ENSP00000390915
PHACTR3	ENST00000359926.7 linkuse as main transcript	c.109+27479T>G		intron_variant		2		ENSP00000353002		Q96KR7-4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

8.14e-7

AC:

AN:

1228180

Hom.:

Cov.:

AF XY:

0.00000166

AC XY:

AN XY:

601134

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:

0.00000101

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Oct 12, 2022

The c.82T>G (p.S28A) alteration is located in exon 1 (coding exon 1) of the PHACTR3 gene. This alteration results from a T to G substitution at nucleotide position 82, causing the serine (S) at amino acid position 28 to be replaced by an alanine (A). 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

0.051

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.49

CADD

Benign

DANN

Benign

0.82

DEOGEN2

Benign

0.0081

.;T

Eigen

Benign

-0.65

Eigen_PC

Benign

-0.52

FATHMM_MKL

Benign

0.23

LIST_S2

Benign

0.26

T;T

M_CAP

Uncertain

0.16

MetaRNN

Benign

0.099

T;T

MetaSVM

Benign

-1.0

MutationTaster

Benign

1.0

D;D;N

PrimateAI

Pathogenic

0.79

PROVEAN

Benign

-1.1

N;N

REVEL

Benign

0.079

Sift

Pathogenic

0.0

D;T

Sift4G

Pathogenic

0.0

D;T

Polyphen

0.0

.;B

Vest4

0.087

MutPred

0.17

Loss of phosphorylation at S28 (P = 0.0107);Loss of phosphorylation at S28 (P = 0.0107);

MVP

0.21

MPC

0.073

ClinPred

0.18

GERP RS

1.5

Varity_R

0.10

gMVP

0.15

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over