Genetic Variant PHACTR1:p.Thr69Met (chr6-12749746-C-T) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_030948.6(PHACTR1):c.206C>T(p.Thr69Met) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T69K) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 27)

Consequence

PHACTR1
NM_030948.6 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.51

Publications

0 publications found

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 Gene-Disease associations (from GenCC):

developmental and epileptic encephalopathy, 70
Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
infantile spasms
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

PHACTR1 links:

ENSG00000309066 (HGNC:):

ENSG00000309066 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_030948.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PHACTR1	NM_030948.6	MANE Select	c.206C>T	p.Thr69Met	missense	Exon 4 of 15	NP_112210.1	Q9C0D0-1
PHACTR1	NM_001322310.2		c.206C>T	p.Thr69Met	missense	Exon 2 of 14	NP_001309239.1
PHACTR1	NM_001374581.2		c.206C>T	p.Thr69Met	missense	Exon 3 of 13	NP_001361510.1	A0A6Q8PG87

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PHACTR1	ENST00000332995.12	TSL:2 MANE Select	c.206C>T	p.Thr69Met	missense	Exon 4 of 15	ENSP00000329880.8	Q9C0D0-1
PHACTR1	ENST00000379348.3	TSL:1	n.383C>T		non_coding_transcript_exon	Exon 3 of 4
PHACTR1	ENST00000674595.1		c.206C>T	p.Thr69Met	missense	Exon 3 of 13	ENSP00000502157.1	A0A6Q8PG87

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00

AC:

AN:

241634

AF XY:

0.00

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.54

BayesDel_addAF

Uncertain

0.048

BayesDel_noAF

Benign

-0.17

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.023

Eigen

Uncertain

0.48

Eigen_PC

Uncertain

0.48

FATHMM_MKL

Uncertain

0.88

M_CAP

Pathogenic

0.40

MetaRNN

Uncertain

0.67

MetaSVM

Benign

-0.82

MutationAssessor

Benign

0.90

PhyloP100

5.5

PrimateAI

Pathogenic

0.89

PROVEAN

Benign

-0.96

REVEL

Benign

0.23

Sift

Benign

0.15

Sift4G

Benign

0.18

Polyphen

1.0

Vest4

0.69

MutPred

0.30

Gain of catalytic residue at T69 (P = 0.015)

MVP

0.65

MPC

2.3

ClinPred

0.95

GERP RS

4.6

PromoterAI

0.041

Neutral

(source)

Varity_R

0.22

gMVP

0.38

Mutation Taster

=45/55

disease causing

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over