12-19129829-C-T

Variant names:

• chr12-19129829-C-T
• rs139525088
• NM_001256470.2:c.30C>T

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_Moderate BP6_Moderate BP7 BS2

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
• Clinical Significance: Likely benign criteria provided, single submitter B:2
• Conservation: PhyloP100: 0.207

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]

ACMG classification

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 rank	MANE	Protein	UniProt
PLEKHA5	NM_001256470.2	c.30C>T	p.Ile10Ile	synonymous_variant	Exon 1 of 32	ENST00000429027.7	NP_001243399.1

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.00264 AC: 400 AN: 151798 Hom.: 1 Cov.: 30

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.: 1 AF XY: 0.00223 AC XY: 290 AN XY: 129836

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.: 9 Cov.: 31 AF XY: 0.00237 AC XY: 1714 AN XY: 722980

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.: 1 Cov.: 30 AF XY: 0.00288 AC XY: 214 AN XY: 74242

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.: 1

Bravo AF: 0.00192

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

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	14
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

Other links and lift over

dbSNP: rs139525088; hg19: chr12-19282763;