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GeneBe

6-12749741-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.201C>T(p.Ser67=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00138 in 1,611,934 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 ( 0 hom., cov: 27)
Exomes 𝑓: 0.0014 ( 6 hom. )

Consequence

PHACTR1
NM_030948.6 synonymous

Scores

2

Clinical Significance

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

Conservation

PhyloP100: -0.130
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=-0.26).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 6-12749741-C-T is Benign according to our data. Variant chr6-12749741-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2656233.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=-0.13 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 205 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
PHACTR1NM_030948.6 linkuse as main transcriptc.201C>T p.Ser67= synonymous_variant 4/15 ENST00000332995.12

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
PHACTR1ENST00000332995.12 linkuse as main transcriptc.201C>T p.Ser67= synonymous_variant 4/152 NM_030948.6 P3Q9C0D0-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00135
AC:
205
AN:
151638
Hom.:
0
Cov.:
27
show subpopulations
Gnomad AFR
AF:
0.000194
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000458
Gnomad ASJ
AF:
0.00115
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000625
Gnomad FIN
AF:
0.00568
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00180
Gnomad OTH
AF:
0.000480
GnomAD3 exomes
AF:
0.00134
AC:
323
AN:
241082
Hom.:
1
AF XY:
0.00143
AC XY:
189
AN XY:
132364
show subpopulations
Gnomad AFR exome
AF:
0.0000678
Gnomad AMR exome
AF:
0.000379
Gnomad ASJ exome
AF:
0.00173
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000558
Gnomad FIN exome
AF:
0.00371
Gnomad NFE exome
AF:
0.00169
Gnomad OTH exome
AF:
0.00288
GnomAD4 exome
AF:
0.00139
AC:
2024
AN:
1460188
Hom.:
6
Cov.:
33
AF XY:
0.00143
AC XY:
1036
AN XY:
726400
show subpopulations
Gnomad4 AFR exome
AF:
0.000418
Gnomad4 AMR exome
AF:
0.000492
Gnomad4 ASJ exome
AF:
0.00138
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000661
Gnomad4 FIN exome
AF:
0.00427
Gnomad4 NFE exome
AF:
0.00143
Gnomad4 OTH exome
AF:
0.00118
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00135
AC:
205
AN:
151746
Hom.:
0
Cov.:
27
AF XY:
0.00154
AC XY:
114
AN XY:
74176
show subpopulations
Gnomad4 AFR
AF:
0.000193
Gnomad4 AMR
AF:
0.000458
Gnomad4 ASJ
AF:
0.00115
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000626
Gnomad4 FIN
AF:
0.00568
Gnomad4 NFE
AF:
0.00180
Gnomad4 OTH
AF:
0.000475
Alfa
AF:
0.00166
Hom.:
2
Bravo
AF:
0.00101
EpiCase
AF:
0.00251
EpiControl
AF:
0.00154

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 SciencesAug 27, 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 TuebingenApr 01, 2024PHACTR1: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.26
Cadd
Benign
14
Dann
Benign
0.97

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.

Other links and lift over

dbSNP: rs199546311; hg19: chr6-12749973; API