chr12-19150838-T-C

Position:

• chr12-19150838-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001256470.2(PLEKHA5):​c.227+18388T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.668 in 152,054 control chromosomes in the GnomAD database, including 37,319 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.67 (37313 hom., cov: 31)
  • Exomes 𝑓: 0.61 (6 hom.)
• Consequence: PLEKHA5 NM_001256470.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.269

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.828 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLEKHA5	NM_001256470.2	c.227+18388T>C		intron_variant		ENST00000429027.7	NP_001243399.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PLEKHA5	ENST00000429027.7	c.227+18388T>C		intron_variant		1	NM_001256470.2	ENSP00000404296	A2
	ENST00000501211.2	n.1570T>C		non_coding_transcript_exon_variant	2/2	1

Frequencies

GnomAD3 genomes AF: 0.669 AC: 101579 AN: 151908 Hom.: 37320 Cov.: 31

Gnomad AFR AF: 0.345

Gnomad AMI AF: 0.658

Gnomad AMR AF: 0.656

Gnomad ASJ AF: 0.728

Gnomad EAS AF: 0.650

Gnomad SAS AF: 0.741

Gnomad FIN AF: 0.836

Gnomad MID AF: 0.674

Gnomad NFE AF: 0.834

Gnomad OTH AF: 0.702

GnomAD4 exome AF: 0.607 AC: 17 AN: 28 Hom.: 6 Cov.: 0 AF XY: 0.500 AC XY: 9 AN XY: 18

Gnomad4 AFR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.500

Gnomad4 EAS exome AF: 0.500

Gnomad4 FIN exome AF: 0.500

Gnomad4 NFE exome AF: 0.700

GnomAD4 genome AF: 0.668 AC: 101603 AN: 152026 Hom.: 37313 Cov.: 31 AF XY: 0.666 AC XY: 49512 AN XY: 74334

Gnomad4 AFR AF: 0.345

Gnomad4 AMR AF: 0.656

Gnomad4 ASJ AF: 0.728

Gnomad4 EAS AF: 0.649

Gnomad4 SAS AF: 0.742

Gnomad4 FIN AF: 0.836

Gnomad4 NFE AF: 0.834

Gnomad4 OTH AF: 0.701

Alfa AF: 0.792 Hom.: 47516

Bravo AF: 0.641

Asia WGS AF: 0.654 AC: 2275 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	4.9
DANN	Benign	0.84

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: rs1514831; hg19: chr12-19303772;