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GeneBe

12-19274579-A-G

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_001256470.2(PLEKHA5):c.909A>G(p.Arg303=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0117 in 1,613,522 control chromosomes in the GnomAD database, including 126 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0081 ( 6 hom., cov: 32)
Exomes 𝑓: 0.012 ( 120 hom. )

Consequence

PLEKHA5
NM_001256470.2 synonymous

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.68
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -17 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=-0.54).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 12-19274579-A-G is Benign according to our data. Variant chr12-19274579-A-G is described in ClinVar as [Benign]. Clinvar id is 781698.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=1.68 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 Homozygotes in GnomAd at 6 gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
PLEKHA5NM_001256470.2 linkuse as main transcriptc.909A>G p.Arg303= synonymous_variant 11/32 ENST00000429027.7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
PLEKHA5ENST00000429027.7 linkuse as main transcriptc.909A>G p.Arg303= synonymous_variant 11/321 NM_001256470.2 A2Q9HAU0-6

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00813
AC:
1237
AN:
152204
Hom.:
6
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00256
Gnomad AMI
AF:
0.0175
Gnomad AMR
AF:
0.00988
Gnomad ASJ
AF:
0.000288
Gnomad EAS
AF:
0.000192
Gnomad SAS
AF:
0.00436
Gnomad FIN
AF:
0.00151
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0134
Gnomad OTH
AF:
0.00718
GnomAD3 exomes
AF:
0.00736
AC:
1846
AN:
250786
Hom.:
7
AF XY:
0.00789
AC XY:
1070
AN XY:
135598
show subpopulations
Gnomad AFR exome
AF:
0.00166
Gnomad AMR exome
AF:
0.00548
Gnomad ASJ exome
AF:
0.000993
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00634
Gnomad FIN exome
AF:
0.00204
Gnomad NFE exome
AF:
0.0118
Gnomad OTH exome
AF:
0.00769
GnomAD4 exome
AF:
0.0121
AC:
17661
AN:
1461200
Hom.:
120
Cov.:
31
AF XY:
0.0120
AC XY:
8700
AN XY:
726968
show subpopulations
Gnomad4 AFR exome
AF:
0.00204
Gnomad4 AMR exome
AF:
0.00535
Gnomad4 ASJ exome
AF:
0.00107
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00714
Gnomad4 FIN exome
AF:
0.00210
Gnomad4 NFE exome
AF:
0.0143
Gnomad4 OTH exome
AF:
0.0104
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00812
AC:
1237
AN:
152322
Hom.:
6
Cov.:
32
AF XY:
0.00773
AC XY:
576
AN XY:
74480
show subpopulations
Gnomad4 AFR
AF:
0.00255
Gnomad4 AMR
AF:
0.00987
Gnomad4 ASJ
AF:
0.000288
Gnomad4 EAS
AF:
0.000193
Gnomad4 SAS
AF:
0.00457
Gnomad4 FIN
AF:
0.00151
Gnomad4 NFE
AF:
0.0134
Gnomad4 OTH
AF:
0.00710
Alfa
AF:
0.0101
Hom.:
5
Bravo
AF:
0.00806
Asia WGS
AF:
0.00375
AC:
13
AN:
3478
EpiCase
AF:
0.0129
EpiControl
AF:
0.0117

ClinVar

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

Submissions by phenotype

PLEKHA5-related disorder Benign:1
Benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact SciencesMar 29, 2019This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -
not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeMar 29, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.54
Cadd
Benign
11
Dann
Benign
0.64

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: rs61755451; hg19: chr12-19427513; API