chr12-19130115-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001256470.2(PLEKHA5):​c.154C>T​(p.Arg52Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000167 in 1,579,008 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00016 ( 0 hom., cov: 30)
Exomes 𝑓: 0.00017 ( 0 hom. )

Consequence

PLEKHA5
NM_001256470.2 missense

Scores

3
6
10

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.585
Variant links:
Genes affected
PLEKHA5 (HGNC:30036): (pleckstrin homology domain containing A5) Predicted to enable phosphatidylinositol phosphate binding activity. Predicted to act upstream of or within reproductive system development. Located in cytosol and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.16403571).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PLEKHA5NM_001256470.2 linkc.154C>T p.Arg52Trp missense_variant Exon 2 of 32 ENST00000429027.7 NP_001243399.1 Q9HAU0-6

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
PLEKHA5ENST00000429027.7 linkc.154C>T p.Arg52Trp missense_variant Exon 2 of 32 1 NM_001256470.2 ENSP00000404296.2 Q9HAU0-6

Frequencies

GnomAD3 genomes
AF:
0.000165
AC:
25
AN:
151886
Hom.:
0
Cov.:
30
show subpopulations
Gnomad AFR
AF:
0.0000242
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000655
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.000471
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000265
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000163
AC:
31
AN:
190538
Hom.:
0
AF XY:
0.000154
AC XY:
16
AN XY:
103790
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000347
Gnomad ASJ exome
AF:
0.000116
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.000470
Gnomad NFE exome
AF:
0.000242
Gnomad OTH exome
AF:
0.000208
GnomAD4 exome
AF:
0.000167
AC:
239
AN:
1427122
Hom.:
0
Cov.:
31
AF XY:
0.000148
AC XY:
105
AN XY:
707444
show subpopulations
Gnomad4 AFR exome
AF:
0.0000317
Gnomad4 AMR exome
AF:
0.0000245
Gnomad4 ASJ exome
AF:
0.0000397
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.000319
Gnomad4 NFE exome
AF:
0.000197
Gnomad4 OTH exome
AF:
0.0000677
GnomAD4 genome
AF:
0.000165
AC:
25
AN:
151886
Hom.:
0
Cov.:
30
AF XY:
0.000175
AC XY:
13
AN XY:
74154
show subpopulations
Gnomad4 AFR
AF:
0.0000242
Gnomad4 AMR
AF:
0.0000655
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.000471
Gnomad4 NFE
AF:
0.000265
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000307
Hom.:
0
Bravo
AF:
0.0000642
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000120
AC:
1
ExAC
AF:
0.000194
AC:
23

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Feb 08, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.154C>T (p.R52W) alteration is located in exon 2 (coding exon 2) of the PLEKHA5 gene. This alteration results from a C to T substitution at nucleotide position 154, causing the arginine (R) at amino acid position 52 to be replaced by a tryptophan (W). 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
Pathogenic
0.70
BayesDel_addAF
Benign
-0.34
T
BayesDel_noAF
Benign
-0.37
CADD
Pathogenic
29
DANN
Uncertain
1.0
DEOGEN2
Benign
0.0047
.;.;T;.
Eigen
Uncertain
0.35
Eigen_PC
Uncertain
0.30
FATHMM_MKL
Benign
0.36
N
LIST_S2
Uncertain
0.91
D;D;D;D
M_CAP
Pathogenic
0.91
D
MetaRNN
Benign
0.16
T;T;T;T
MetaSVM
Benign
-1.2
T
MutationAssessor
Uncertain
2.3
M;M;M;M
PrimateAI
Pathogenic
0.90
D
PROVEAN
Benign
-2.1
N;N;N;N
REVEL
Benign
0.21
Sift
Benign
0.18
T;D;D;D
Sift4G
Uncertain
0.029
D;D;D;D
Polyphen
1.0
.;.;D;D
Vest4
0.34
MVP
0.26
MPC
1.4
ClinPred
0.18
T
GERP RS
3.6
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.14
gMVP
0.71

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: rs374080735; hg19: chr12-19283049; API