Variant 12-19129829-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_ModerateBP6_ModerateBP7BS2

The NM_001256470.2(PLEKHA5):c.30C>T(p.Ile10=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00242 in 1,604,858 control chromosomes in the GnomAD database, including 10 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0026 ( 1 hom., cov: 30)

Exomes 𝑓: 0.0024 ( 9 hom. )

Consequence

PLEKHA5
NM_001256470.2 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:2

Conservation

PhyloP100: 0.207

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]

PLEKHA5 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.21).

BP6

Variant 12-19129829-C-T is Benign according to our data. Variant chr12-19129829-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2642769.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=0.207 with no splicing effect.

BS2

High Homozygotes in GnomAdExome4 at 9 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PLEKHA5	NM_001256470.2 linkuse as main transcript	c.30C>T	p.Ile10=	synonymous_variant	1/32	ENST00000429027.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PLEKHA5	ENST00000429027.7 linkuse as main transcript	c.30C>T	p.Ile10=	synonymous_variant	1/32	1	NM_001256470.2	A2	Q9HAU0-6

Frequencies

GnomAD3 genomes

AF:

0.00264

AC:

400

AN:

151798

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000411

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00236

Gnomad ASJ

AF:

0.000577

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00833

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00367

Gnomad OTH

AF:

0.00383

GnomAD3 exomes

AF:

0.00224

AC:

531

AN:

236738

Hom.:

AF XY:

0.00223

AC XY:

290

AN XY:

129836

show subpopulations

Gnomad AFR exome

AF:

0.000142

Gnomad AMR exome

AF:

0.000692

Gnomad ASJ exome

AF:

0.000831

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000335

Gnomad FIN exome

AF:

0.00672

Gnomad NFE exome

AF:

0.00322

Gnomad OTH exome

AF:

0.00228

GnomAD4 exome

AF:

0.00239

AC:

3479

AN:

1452956

Hom.:

Cov.:

AF XY:

0.00237

AC XY:

1714

AN XY:

722980

show subpopulations

Gnomad4 AFR exome

AF:

0.000123

Gnomad4 AMR exome

AF:

0.000793

Gnomad4 ASJ exome

AF:

0.000890

Gnomad4 EAS exome

AF:

0.0000258

Gnomad4 SAS exome

AF:

0.000117

Gnomad4 FIN exome

AF:

0.00687

Gnomad4 NFE exome

AF:

0.00264

Gnomad4 OTH exome

AF:

0.00195

GnomAD4 genome

AF:

0.00263

AC:

400

AN:

151902

Hom.:

Cov.:

AF XY:

0.00288

AC XY:

214

AN XY:

74242

show subpopulations

Gnomad4 AFR

AF:

0.000410

Gnomad4 AMR

AF:

0.00235

Gnomad4 ASJ

AF:

0.000577

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00833

Gnomad4 NFE

AF:

0.00367

Gnomad4 OTH

AF:

0.00380

Alfa

AF:

0.00338

Hom.:

Bravo

AF:

0.00192

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

PLEKHA5-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Mar 12, 2019

This 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 submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jul 01, 2022

PLEKHA5: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.21

CADD

Benign

DANN

Uncertain

0.98

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over