dbSNP rs865912633: PHACTR3:c.-376G>T (chr20-59577524-G-T) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001199505.1(PHACTR3):c.16G>T(p.Gly6Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000299 in 1,149,296 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. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0016 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00011 ( 0 hom. )

Consequence

PHACTR3
NM_001199505.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.06714946).

BS2

High AC in GnomAd4 at 234 AD gene.

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>T	p.Gly6Trp	missense	Exon 1 of 13	NP_001186434.1	Q96KR7-4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PHACTR3	ENST00000944653.1		c.-376G>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 11	ENSP00000614712.1
PHACTR3	ENST00000359926.7	TSL:2	c.16G>T	p.Gly6Trp	missense	Exon 1 of 13	ENSP00000353002.3	Q96KR7-4
PHACTR3	ENST00000944653.1		c.-376G>T		5_prime_UTR	Exon 1 of 11	ENSP00000614712.1

Frequencies

GnomAD3 genomes

AF:

0.00157

AC:

234

AN:

149352

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00530

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000533

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00145

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000149

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.000110

AC:

110

AN:

999836

Hom.:

Cov.:

AF XY:

0.000119

AC XY:

AN XY:

470790

show subpopulations

African (AFR)

AF:

0.00429

AC:

AN:

20050

American (AMR)

AF:

0.000177

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:

0.000212

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:

0.00000230

AC:

AN:

868768

Other (OTH)

AF:

0.000450

AC:

AN:

37774

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00157

AC:

234

AN:

149460

Hom.:

Cov.:

AF XY:

0.00156

AC XY:

114

AN XY:

72928

show subpopulations

African (AFR)

AF:

0.00528

AC:

218

AN:

41264

American (AMR)

AF:

0.000532

AC:

AN:

15038

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3440

East Asian (EAS)

AF:

0.00

AC:

AN:

5138

South Asian (SAS)

AF:

0.00145

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9472

Middle Eastern (MID)

AF:

0.00

AC:

AN:

290

European-Non Finnish (NFE)

AF:

0.0000149

AC:

AN:

67002

Other (OTH)

AF:

0.00

AC:

AN:

2080

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000143

Hom.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.29

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.59

CADD

Benign

(source)

DANN

Benign

0.94

Eigen

Benign

-0.12

Eigen_PC

Benign

-0.20

FATHMM_MKL

Benign

0.38

LIST_S2

Benign

0.34

M_CAP

Uncertain

0.15

MetaRNN

Benign

0.067

MetaSVM

Benign

-1.1

PhyloP100

1.0

PROVEAN

Benign

0.070

REVEL

Benign

0.066

Sift

Uncertain

0.020

Sift4G

Uncertain

0.047

Vest4

0.42

MutPred

0.36

Loss of methylation at R2 (P = 0.0388)

MVP

0.068

ClinPred

0.36

GERP RS

1.5

PromoterAI

0.071

Neutral

(source)

Mutation Taster

=96/4

polymorphism

(source)

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over