Variant chr6-12749704-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 1P and 8B. PP2BP4_StrongBS2

The NM_030948.6(PHACTR1):c.164T>C(p.Ile55Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000931 in 1,611,294 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 27)

Exomes 𝑓: 0.0000089 ( 0 hom. )

Consequence

PHACTR1
NM_030948.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.28

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 -7 ACMG points.

PP2

Missense variant in gene, where missense usually causes diseases (based on misZ statistic), PHACTR1. . Gene score misZ 0.708 (greater than the threshold 3.09). Trascript score misZ 3.1944 (greater than threshold 3.09). GenCC has associacion of gene with West syndrome, developmental and epileptic encephalopathy, 70.

BP4

Computational evidence support a benign effect (MetaRNN=0.06192878).

BS2

High AC in GnomAdExome4 at 13 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PHACTR1	NM_030948.6 linkuse as main transcript	c.164T>C	p.Ile55Thr	missense_variant	4/15	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.164T>C	p.Ile55Thr	missense_variant	4/15	2	NM_030948.6	ENSP00000329880	P3	Q9C0D0-1

Frequencies

GnomAD3 genomes

AF:

0.0000132

AC:

AN:

151232

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000487

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000165

AC:

AN:

242844

Hom.:

AF XY:

0.0000150

AC XY:

AN XY:

133248

show subpopulations

Gnomad AFR exome

AF:

0.000136

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000328

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000923

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000890

AC:

AN:

1460062

Hom.:

Cov.:

AF XY:

0.0000124

AC XY:

AN XY:

726292

show subpopulations

Gnomad4 AFR exome

AF:

0.000179

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000464

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000180

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000132

AC:

AN:

151232

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

73806

show subpopulations

Gnomad4 AFR

AF:

0.0000487

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.0000227

ExAC

AF:

0.0000166

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 08, 2022

The c.164T>C (p.I55T) alteration is located in exon 4 (coding exon 2) of the PHACTR1 gene. This alteration results from a T to C substitution at nucleotide position 164, causing the isoleucine (I) at amino acid position 55 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.089

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.46

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.016

T;.;T

Eigen

Benign

-0.71

Eigen_PC

Benign

-0.53

FATHMM_MKL

Benign

0.17

M_CAP

Uncertain

0.12

MetaRNN

Benign

0.062

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.34

N;N;.

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Uncertain

0.79

PROVEAN

Benign

-0.34

N;N;N

REVEL

Benign

0.13

Sift

Benign

0.27

T;T;T

Sift4G

Benign

0.36

T;T;T

Polyphen

0.0020

B;B;B

Vest4

0.22

MutPred

0.17

Gain of phosphorylation at I55 (P = 0.0024);Gain of phosphorylation at I55 (P = 0.0024);Gain of phosphorylation at I55 (P = 0.0024);

MVP

0.18

MPC

1.8

ClinPred

0.083

GERP RS

4.7

Varity_R

0.087

gMVP

0.095

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