Variant chr6-13286236-G-GT details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 2P and 10B. PVS1_ModerateBP6_ModerateBS1BS2

The NM_001374581.2(PHACTR1):c.1751dupT(p.Leu585fs) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0111 in 1,370,204 control chromosomes in the GnomAD database, including 2 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0019 ( 1 hom., cov: 32)

Exomes 𝑓: 0.012 ( 1 hom. )

Consequence

PHACTR1
NM_001374581.2 frameshift

Scores

Not classified

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.588

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

PVS1

Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most exon, not predicted to undergo nonsense mediated mRNA decay. Fraction of 0.0218 CDS is truncated, and there are 0 pathogenic variants in the truncated region.

BP6

Variant 6-13286236-G-GT is Benign according to our data. Variant chr6-13286236-G-GT is described in ClinVar as [Likely_benign]. Clinvar id is 3024709.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population amr. gnomad4_exome allele frequency = 0.0122 (14877/1221312) while in subpopulation AMR AF= 0.0168 (432/25712). AF 95% confidence interval is 0.0155. There are 1 homozygotes in gnomad4_exome. There are 7465 alleles in male gnomad4_exome subpopulation. Median coverage is 29. This position pass quality control queck.

BS2

High AC in GnomAd4 at 278 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PHACTR1	NM_030948.6 linkuse as main transcript	c.1727+24dupT		intron_variant		ENST00000332995.12	NP_112210.1	Q9C0D0-1B4DHU0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PHACTR1	ENST00000332995.12 linkuse as main transcript	c.1727+24dupT		intron_variant		2	NM_030948.6	ENSP00000329880.8		Q9C0D0-1

Frequencies

GnomAD3 genomes

AF:

0.00188

AC:

279

AN:

148780

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00119

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00437

Gnomad ASJ

AF:

0.00117

Gnomad EAS

AF:

0.00570

Gnomad SAS

AF:

0.00171

Gnomad FIN

AF:

0.000300

Gnomad MID

AF:

0.00637

Gnomad NFE

AF:

0.00167

Gnomad OTH

AF:

0.00393

GnomAD4 exome

AF:

0.0122

AC:

14877

AN:

1221312

Hom.:

Cov.:

AF XY:

0.0124

AC XY:

7465

AN XY:

602202

show subpopulations

Gnomad4 AFR exome

AF:

0.0114

Gnomad4 AMR exome

AF:

0.0168

Gnomad4 ASJ exome

AF:

0.0129

Gnomad4 EAS exome

AF:

0.0152

Gnomad4 SAS exome

AF:

0.0151

Gnomad4 FIN exome

AF:

0.00691

Gnomad4 NFE exome

AF:

0.0120

Gnomad4 OTH exome

AF:

0.0126

GnomAD4 genome

AF:

0.00187

AC:

278

AN:

148892

Hom.:

Cov.:

AF XY:

0.00180

AC XY:

131

AN XY:

72616

show subpopulations

Gnomad4 AFR

AF:

0.00118

Gnomad4 AMR

AF:

0.00437

Gnomad4 ASJ

AF:

0.00117

Gnomad4 EAS

AF:

0.00552

Gnomad4 SAS

AF:

0.00171

Gnomad4 FIN

AF:

0.000300

Gnomad4 NFE

AF:

0.00167

Gnomad4 OTH

AF:

0.00389

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

Dec 01, 2023

PHACTR1: BS1 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

Name

Calibrated prediction

Score

Prediction

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