Genetic Variant NM_001256470.2:c.30C>T (chr12-19129829-C-T) – ACMG Classification: Benign (-9 pts)

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_ModerateBP6_ModerateBP7BS2

The NM_001256470.2(PLEKHA5):c.30C>T(p.Ile10Ile) 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

Publications

0 publications found

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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
PLEKHA5	NM_001256470.2 link	c.30C>T	p.Ile10Ile	synonymous_variant	Exon 1 of 32	ENST00000429027.7	NP_001243399.1	Q9HAU0-6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLEKHA5	ENST00000429027.7 link	c.30C>T	p.Ile10Ile	synonymous_variant	Exon 1 of 32	1	NM_001256470.2	ENSP00000404296.2		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

GnomAD2 exomes

AF:

0.00224

AC:

531

AN:

236738

AF XY:

0.00223

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 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

African (AFR)

AF:

0.000123

AC:

AN:

32448

American (AMR)

AF:

0.000793

AC:

AN:

44140

Ashkenazi Jewish (ASJ)

AF:

0.000890

AC:

AN:

25832

East Asian (EAS)

AF:

0.0000258

AC:

AN:

38720

South Asian (SAS)

AF:

0.000117

AC:

AN:

85484

European-Finnish (FIN)

AF:

0.00687

AC:

360

AN:

52366

Middle Eastern (MID)

AF:

0.000174

AC:

AN:

5738

European-Non Finnish (NFE)

AF:

0.00264

AC:

2928

AN:

1108272

Other (OTH)

AF:

0.00195

AC:

117

AN:

59956

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.460

Heterozygous variant carriers

157

314

472

629

786

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00263

AC:

400

AN:

151902

Hom.:

Cov.:

AF XY:

0.00288

AC XY:

214

AN XY:

74242

show subpopulations

African (AFR)

AF:

0.000410

AC:

AN:

41490

American (AMR)

AF:

0.00235

AC:

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.000577

AC:

AN:

3464

East Asian (EAS)

AF:

0.00

AC:

AN:

5090

South Asian (SAS)

AF:

0.00

AC:

AN:

4814

European-Finnish (FIN)

AF:

0.00833

AC:

AN:

10564

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.00367

AC:

249

AN:

67870

Other (OTH)

AF:

0.00380

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

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

Mar 12, 2019

PreventionGenetics, part of Exact Sciences

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

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

Jul 01, 2022

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

PLEKHA5: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.21

CADD

Benign

(source)

DANN

Uncertain

0.98

PhyloP100

0.21

PromoterAI

0.0015

Neutral

(source)

Mutation Taster

=97/3

polymorphism

(source)

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

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NM_001256470.2:c.30C>T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over