dbSNP rs961562111: PHACTR3:p.Gly7Trp (chr20-59577527-G-T) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_001199505.1(PHACTR3):c.19G>T(p.Gly7Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000233 in 1,156,980 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 0.00014 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000060 ( 0 hom. )

Consequence

PHACTR3
NM_001199505.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.694

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: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.25971).

BS2

High AC in GnomAd4 at 21 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.19G>T	p.Gly7Trp	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.19G>T	p.Gly7Trp	missense	Exon 1 of 13	ENSP00000353002.3	Q96KR7-4
	PHACTR3	ENST00000944653.1		c.-373G>T		5_prime_UTR	Exon 1 of 11	ENSP00000614712.1

Frequencies

GnomAD3 genomes

AF:

0.000140

AC:

AN:

149480

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000413

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000133

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:

0.000972

GnomAD4 exome

AF:

0.00000596

AC:

AN:

1007500

Hom.:

Cov.:

AF XY:

0.00000211

AC XY:

AN XY:

474562

show subpopulations

African (AFR)

AF:

0.000197

AC:

AN:

20316

American (AMR)

AF:

0.00

AC:

AN:

5892

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

11094

East Asian (EAS)

AF:

0.00

AC:

AN:

19708

South Asian (SAS)

AF:

0.00

AC:

AN:

18906

European-Finnish (FIN)

AF:

0.00

AC:

AN:

17098

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2500

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

873736

Other (OTH)

AF:

0.0000523

AC:

AN:

38250

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.442

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:

0.000140

AC:

AN:

149480

Hom.:

Cov.:

AF XY:

0.000151

AC XY:

AN XY:

72884

show subpopulations

African (AFR)

AF:

0.000413

AC:

AN:

41150

American (AMR)

AF:

0.000133

AC:

AN:

15028

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3444

East Asian (EAS)

AF:

0.00

AC:

AN:

5148

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9530

Middle Eastern (MID)

AF:

0.00

AC:

AN:

312

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67070

Other (OTH)

AF:

0.000972

AC:

AN:

2058

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.518

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:

0.00

Hom.:

Bravo

AF:

0.000144

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

0.24

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.56

CADD

Benign

(source)

DANN

Benign

0.96

Eigen

Benign

-0.11

Eigen_PC

Benign

-0.20

FATHMM_MKL

Benign

0.36

LIST_S2

Benign

0.37

M_CAP

Uncertain

0.18

MetaRNN

Benign

0.26

MetaSVM

Benign

-1.1

PhyloP100

0.69

PROVEAN

Benign

-0.13

REVEL

Benign

0.077

Sift

Uncertain

0.0020

Sift4G

Uncertain

0.020

Vest4

0.44

MutPred

0.35

Loss of methylation at R8 (P = 0.0295)

MVP

0.082

ClinPred

0.31

GERP RS

1.5

PromoterAI

0.20

Neutral

(source)

Mutation Taster

=97/3

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