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GeneBe

6-13053411-C-T

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_ModerateBP6_Very_StrongBP7BS2

The NM_030948.6(PHACTR1):c.297C>T(p.Val99=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00186 in 1,613,372 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0014 ( 1 hom., cov: 33)
Exomes 𝑓: 0.0019 ( 5 hom. )

Consequence

PHACTR1
NM_030948.6 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.180
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.4).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 6-13053411-C-T is Benign according to our data. Variant chr6-13053411-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1676009.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-0.18 with no splicing effect.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High AC in GnomAd at 215 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
PHACTR1NM_030948.6 linkuse as main transcriptc.297C>T p.Val99= synonymous_variant 5/15 ENST00000332995.12

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
PHACTR1ENST00000332995.12 linkuse as main transcriptc.297C>T p.Val99= synonymous_variant 5/152 NM_030948.6 P3Q9C0D0-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00141
AC:
215
AN:
152166
Hom.:
1
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.000797
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00308
Gnomad ASJ
AF:
0.00375
Gnomad EAS
AF:
0.000192
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.000188
Gnomad MID
AF:
0.00316
Gnomad NFE
AF:
0.00172
Gnomad OTH
AF:
0.000478
GnomAD3 exomes
AF:
0.00138
AC:
341
AN:
247898
Hom.:
1
AF XY:
0.00129
AC XY:
173
AN XY:
134534
show subpopulations
Gnomad AFR exome
AF:
0.000713
Gnomad AMR exome
AF:
0.00225
Gnomad ASJ exome
AF:
0.00409
Gnomad EAS exome
AF:
0.000112
Gnomad SAS exome
AF:
0.0000986
Gnomad FIN exome
AF:
0.000279
Gnomad NFE exome
AF:
0.00170
Gnomad OTH exome
AF:
0.00167
GnomAD4 exome
AF:
0.00191
AC:
2793
AN:
1461088
Hom.:
5
Cov.:
30
AF XY:
0.00179
AC XY:
1299
AN XY:
726782
show subpopulations
Gnomad4 AFR exome
AF:
0.000956
Gnomad4 AMR exome
AF:
0.00199
Gnomad4 ASJ exome
AF:
0.00364
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.000151
Gnomad4 FIN exome
AF:
0.000169
Gnomad4 NFE exome
AF:
0.00219
Gnomad4 OTH exome
AF:
0.00189
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00141
AC:
215
AN:
152284
Hom.:
1
Cov.:
33
AF XY:
0.00132
AC XY:
98
AN XY:
74482
show subpopulations
Gnomad4 AFR
AF:
0.000794
Gnomad4 AMR
AF:
0.00307
Gnomad4 ASJ
AF:
0.00375
Gnomad4 EAS
AF:
0.000193
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.000188
Gnomad4 NFE
AF:
0.00172
Gnomad4 OTH
AF:
0.000473
Alfa
AF:
0.00172
Hom.:
0
Bravo
AF:
0.00161
EpiCase
AF:
0.00180
EpiControl
AF:
0.00214

ClinVar

Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

PHACTR1-related disorder Benign:1
Likely benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact SciencesNov 07, 2019This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -
not provided Benign:1
Likely benign, criteria provided, single submitterclinical testingCeGaT Center for Human Genetics TuebingenNov 01, 2022PHACTR1: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.40
Cadd
Benign
8.3
Dann
Benign
0.64

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.040
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.

Other links and lift over

dbSNP: rs141282814; hg19: chr6-13053643; COSMIC: COSV100275274; COSMIC: COSV100275274; API