rs185255302

Variant names:

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 1P and 10B. PP3BP6_ModerateBS1BS2

The NM_030948.6(PHACTR1):c.1392-4G>A variant causes a splice region, intron change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00231 in 1,614,048 control chromosomes in the GnomAD database, including 34 homozygotes. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0023 ( 3 hom., cov: 33)

Exomes 𝑓: 0.0023 ( 31 hom. )

Consequence

PHACTR1
NM_030948.6 splice_region, intron

Scores

Splicing: ADA: 0.9941

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 8.07

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:

TBC1D7-LOC100130357 (HGNC:):

TBC1D7-LOC100130357 links:

TBC1D7 (HGNC:21066): (TBC1 domain family member 7) This gene encodes a member of the TBC-domain containing protein family. The encoded protein functions as a subunit of the tuberous sclerosis TSC1-TSC2 complex which plays a role in the regulation of cellular growth and differentiation. Mutations in this gene have been associated with autosomal recessive megalencephaly. Alternative splicing results in multiple transcript variants. Naturally occurring readthrough transcription occurs between this locus and downstream LOC100130357. [provided by RefSeq, Jan 2016]

TBC1D7 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

PP3

Splicing scoreres supports a deletorius effect: Scorers claiming Pathogenic: dbscSNV1_ADA, dbscSNV1_RF. No scorers claiming Uncertain. Scorers claiming Benign: max_spliceai.

BP6

Variant 6-13272856-G-A is Benign according to our data. Variant chr6-13272856-G-A is described in ClinVar as [Benign]. Clinvar id is 2656241.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population mid. gnomad4_exome allele frequency = 0.00231 (3381/1461706) while in subpopulation MID AF= 0.0191 (110/5768). AF 95% confidence interval is 0.0162. There are 31 homozygotes in gnomad4_exome. There are 1981 alleles in male gnomad4_exome subpopulation. Median coverage is 30. This position pass quality control queck.

BS2

High AC in GnomAd4 at 343 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PHACTR1	NM_030948.6 link	c.1392-4G>A		splice_region_variant, intron_variant	Intron 10 of 14	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.1392-4G>A		splice_region_variant, intron_variant	Intron 10 of 14	2	NM_030948.6	ENSP00000329880.8		Q9C0D0-1

Frequencies

GnomAD3 genomes

AF:

0.00228

AC:

347

AN:

152224

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000217

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00242

Gnomad ASJ

AF:

0.0222

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0124

Gnomad FIN

AF:

0.0000942

Gnomad MID

AF:

0.0253

Gnomad NFE

AF:

0.00216

Gnomad OTH

AF:

0.00382

GnomAD3 exomes

AF:

0.00388

AC:

968

AN:

249302

Hom.:

AF XY:

0.00455

AC XY:

615

AN XY:

135250

show subpopulations

Gnomad AFR exome

AF:

0.000129

Gnomad AMR exome

AF:

0.00379

Gnomad ASJ exome

AF:

0.0159

Gnomad EAS exome

AF:

0.000111

Gnomad SAS exome

AF:

0.0114

Gnomad FIN exome

AF:

0.0000928

Gnomad NFE exome

AF:

0.00251

Gnomad OTH exome

AF:

0.00644

GnomAD4 exome

AF:

0.00231

AC:

3381

AN:

1461706

Hom.:

Cov.:

AF XY:

0.00272

AC XY:

1981

AN XY:

727138

show subpopulations

Gnomad4 AFR exome

AF:

0.000179

Gnomad4 AMR exome

AF:

0.00338

Gnomad4 ASJ exome

AF:

0.0151

Gnomad4 EAS exome

AF:

0.000151

Gnomad4 SAS exome

AF:

0.0122

Gnomad4 FIN exome

AF:

0.0000749

Gnomad4 NFE exome

AF:

0.00129

Gnomad4 OTH exome

AF:

0.00371

GnomAD4 genome

AF:

0.00225

AC:

343

AN:

152342

Hom.:

Cov.:

AF XY:

0.00239

AC XY:

178

AN XY:

74494

show subpopulations

Gnomad4 AFR

AF:

0.000216

Gnomad4 AMR

AF:

0.00242

Gnomad4 ASJ

AF:

0.0222

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.0120

Gnomad4 FIN

AF:

0.0000942

Gnomad4 NFE

AF:

0.00216

Gnomad4 OTH

AF:

0.00331

Alfa

AF:

0.00347

Hom.:

Bravo

AF:

0.00210

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.00156

AC:

ESP6500AA

AF:

0.000797

AC:

ESP6500EA

AF:

0.00292

AC:

ExAC

AF:

0.00408

AC:

493

Asia WGS

AF:

0.00202

AC:

AN:

3478

EpiCase

AF:

0.00414

EpiControl

AF:

0.00427

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Jul 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

PHACTR1: BP4, BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.15

CADD

Benign

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.020

T;T

Eigen

Uncertain

0.42

Eigen_PC

Uncertain

0.51

FATHMM_MKL

Uncertain

0.94

MetaRNN

Benign

0.010

T;T

MetaSVM

Benign

-0.51

PROVEAN

Benign

-0.36

N;N

REVEL

Benign

0.22

Sift

Benign

0.084

T;D

Sift4G

Uncertain

0.028

D;D

Vest4

0.72

MVP

0.62

ClinPred

0.072

GERP RS

5.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Pathogenic

0.99

dbscSNV1_RF

Pathogenic

0.96

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

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