6-12933813-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

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
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.84

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]

ACMG classification

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 GnomAd at 460 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PHACTR1	NM_030948.6	c.251-119552C>T		intron_variant		ENST00000332995.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PHACTR1	ENST00000332995.12	c.251-119552C>T		intron_variant		2	NM_030948.6	P3

Frequencies

GnomAD3 genomes AF: 0.00302 AC: 460 AN: 152200 Hom.: 2 Cov.: 32

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.: 1 AF XY: 0.00321 AC XY: 426 AN XY: 132512

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.: 21 Cov.: 31 AF XY: 0.00405 AC XY: 2945 AN XY: 726542

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.: 2 Cov.: 32 AF XY: 0.00301 AC XY: 224 AN XY: 74492

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.: 2

Bravo AF: 0.00320

TwinsUK AF: 0.00324 AC: 12

ALSPAC AF: 0.00389 AC: 15

ESP6500AA AF: 0.000571 AC: 1

ESP6500EA AF: 0.00402 AC: 16

ExAC AF: 0.00283 AC: 329

Asia WGS AF: 0.000866 AC: 3 AN: 3478

EpiCase AF: 0.00491

EpiControl AF: 0.00451

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Apr 01, 2024

PHACTR1: BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.63	T
BayesDel_noAF	Benign	-0.67
Cadd	Benign	7.9
Dann	Benign	0.88
DEOGEN2	Benign	0.014	T
Eigen	Benign	-0.47
Eigen_PC	Benign	-0.65
FATHMM_MKL	Benign	0.039	N
M_CAP	Benign	0.0044	T
MetaRNN	Benign	0.0061	T
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	1.0	N;N;N
PROVEAN	Benign	-0.10	N
REVEL	Benign	0.066
Sift	Pathogenic	0.0	D
Polyphen		0.76	P
Vest4		0.24
MVP		0.15
MPC		0.031
ClinPred		0.033	T
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

Other links and lift over

dbSNP: rs139710456; hg19: chr6-12934045; COSMIC: COSV105196987;