Variant 6-12933813-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_030948.6(PHACTR1):c.251-119552C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00404 in 1,612,812 control chromosomes in the GnomAD database, including 23 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0030 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0041 ( 21 hom. )

Consequence

PHACTR1
NM_030948.6 intron

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.84

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.00609836).

BP6

Variant 6-12933813-C-T is Benign according to our data. Variant chr6-12933813-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2656234.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 461 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PHACTR1	NM_030948.6 linkuse as main transcript	c.251-119552C>T		intron_variant		ENST00000332995.12	NP_112210.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PHACTR1	ENST00000332995.12 linkuse as main transcript	c.251-119552C>T		intron_variant		2	NM_030948.6	ENSP00000329880	P3	Q9C0D0-1

Frequencies

GnomAD3 genomes

AF:

0.00302

AC:

460

AN:

152200

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000772

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00720

Gnomad ASJ

AF:

0.00432

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000621

Gnomad FIN

AF:

0.000283

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00409

Gnomad OTH

AF:

0.00860

GnomAD3 exomes

AF:

0.00310

AC:

749

AN:

241334

Hom.:

AF XY:

0.00321

AC XY:

426

AN XY:

132512

show subpopulations

Gnomad AFR exome

AF:

0.000771

Gnomad AMR exome

AF:

0.00414

Gnomad ASJ exome

AF:

0.00534

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000626

Gnomad FIN exome

AF:

0.000836

Gnomad NFE exome

AF:

0.00444

Gnomad OTH exome

AF:

0.00503

GnomAD4 exome

AF:

0.00415

AC:

6057

AN:

1460494

Hom.:

Cov.:

AF XY:

0.00405

AC XY:

2945

AN XY:

726542

show subpopulations

Gnomad4 AFR exome

AF:

0.000657

Gnomad4 AMR exome

AF:

0.00427

Gnomad4 ASJ exome

AF:

0.00486

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.000777

Gnomad4 FIN exome

AF:

0.00122

Gnomad4 NFE exome

AF:

0.00478

Gnomad4 OTH exome

AF:

0.00426

GnomAD4 genome

AF:

0.00303

AC:

461

AN:

152318

Hom.:

Cov.:

AF XY:

0.00301

AC XY:

224

AN XY:

74492

show subpopulations

Gnomad4 AFR

AF:

0.000770

Gnomad4 AMR

AF:

0.00719

Gnomad4 ASJ

AF:

0.00432

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000622

Gnomad4 FIN

AF:

0.000283

Gnomad4 NFE

AF:

0.00410

Gnomad4 OTH

AF:

0.00851

Alfa

AF:

0.00395

Hom.:

Bravo

AF:

0.00320

TwinsUK

AF:

0.00324

AC:

ALSPAC

AF:

0.00389

AC:

ESP6500AA

AF:

0.000571

AC:

ESP6500EA

AF:

0.00402

AC:

ExAC

AF:

0.00283

AC:

329

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.00491

EpiControl

AF:

0.00451

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jul 01, 2024

PHACTR1: BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.63

BayesDel_noAF

Benign

-0.67

CADD

Benign

7.9

DANN

Benign

0.88

DEOGEN2

Benign

0.014

Eigen

Benign

-0.47

Eigen_PC

Benign

-0.65

FATHMM_MKL

Benign

0.039

M_CAP

Benign

0.0044

MetaRNN

Benign

0.0061

MetaSVM

Benign

-1.1

MutationTaster

Benign

1.0

N;N;N

PROVEAN

Benign

-0.10

REVEL

Benign

0.066

Sift

Pathogenic

0.0

Polyphen

0.76

Vest4

0.24

MVP

0.15

MPC

0.031

ClinPred

0.033

GERP RS

2.0

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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