dbSNP rs141282814: PHACTR1:p.Val99Val (chr6-13053411-C-T) – ACMG Classification: Benign (-9 pts)

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_ModerateBP6_ModerateBP7BS2

The NM_030948.6(PHACTR1):c.297C>T(p.Val99Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00186 in 1,613,372 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0014 ( 1 hom., cov: 33)

Exomes 𝑓: 0.0019 ( 5 hom. )

Consequence

PHACTR1
NM_030948.6 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:2

Conservation

PhyloP100: -0.180

Variant links:

Genes affected

PHACTR1 (HGNC:20990): (phosphatase and actin regulator 1) The protein encoded by this gene is a member of the phosphatase and actin regulator family of proteins. This family member can bind actin and regulate the reorganization of the actin cytoskeleton. It plays a role in tubule formation and in endothelial cell survival. Polymorphisms in this gene are associated with susceptibility to myocardial infarction, coronary artery disease and cervical artery dissection. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Apr 2016]

PHACTR1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.4).

BP6

Variant 6-13053411-C-T is Benign according to our data. Variant chr6-13053411-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1676009.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.18 with no splicing effect.

BS2

High AC in GnomAd4 at 215 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PHACTR1	NM_030948.6 link	c.297C>T	p.Val99Val	synonymous_variant	Exon 5 of 15	ENST00000332995.12	NP_112210.1	Q9C0D0-1B4DHU0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PHACTR1	ENST00000332995.12 link	c.297C>T	p.Val99Val	synonymous_variant	Exon 5 of 15	2	NM_030948.6	ENSP00000329880.8		Q9C0D0-1

Frequencies

GnomAD3 genomes

AF:

0.00141

AC:

215

AN:

152166

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000797

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00308

Gnomad ASJ

AF:

0.00375

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000188

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00172

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.00138

AC:

341

AN:

247898

Hom.:

AF XY:

0.00129

AC XY:

173

AN XY:

134534

show subpopulations

Gnomad AFR exome

AF:

0.000713

Gnomad AMR exome

AF:

0.00225

Gnomad ASJ exome

AF:

0.00409

Gnomad EAS exome

AF:

0.000112

Gnomad SAS exome

AF:

0.0000986

Gnomad FIN exome

AF:

0.000279

Gnomad NFE exome

AF:

0.00170

Gnomad OTH exome

AF:

0.00167

GnomAD4 exome

AF:

0.00191

AC:

2793

AN:

1461088

Hom.:

Cov.:

AF XY:

0.00179

AC XY:

1299

AN XY:

726782

show subpopulations

Gnomad4 AFR exome

AF:

0.000956

Gnomad4 AMR exome

AF:

0.00199

Gnomad4 ASJ exome

AF:

0.00364

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.000151

Gnomad4 FIN exome

AF:

0.000169

Gnomad4 NFE exome

AF:

0.00219

Gnomad4 OTH exome

AF:

0.00189

GnomAD4 genome

AF:

0.00141

AC:

215

AN:

152284

Hom.:

Cov.:

AF XY:

0.00132

AC XY:

AN XY:

74482

show subpopulations

Gnomad4 AFR

AF:

0.000794

Gnomad4 AMR

AF:

0.00307

Gnomad4 ASJ

AF:

0.00375

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000188

Gnomad4 NFE

AF:

0.00172

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.00172

Hom.:

Bravo

AF:

0.00161

EpiCase

AF:

0.00180

EpiControl

AF:

0.00214

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

PHACTR1-related disorder

Benign:1

Nov 07, 2019

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

not provided

Benign:1

Nov 01, 2022

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

PHACTR1: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.40

CADD

Benign

8.3

DANN

Benign

0.64

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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