chr12-19319901-A-G

Position:

• chr12-19319901-A-G

Variant summary

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

The NM_001256470.2(PLEKHA5):​c.2119-120A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0867 in 582,802 control chromosomes in the GnomAD database, including 2,543 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 0.093 (720 hom., cov: 32)
  • Exomes 𝑓: 0.085 (1823 hom.)
• Consequence: PLEKHA5 NM_001256470.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0980

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.116 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLEKHA5	NM_001256470.2	c.2119-120A>G		intron_variant		ENST00000429027.7	NP_001243399.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PLEKHA5	ENST00000429027.7	c.2119-120A>G		intron_variant		1	NM_001256470.2	ENSP00000404296	A2

Frequencies

GnomAD3 genomes AF: 0.0927 AC: 14105 AN: 152124 Hom.: 721 Cov.: 32

Gnomad AFR AF: 0.118

Gnomad AMI AF: 0.354

Gnomad AMR AF: 0.0865

Gnomad ASJ AF: 0.156

Gnomad EAS AF: 0.0204

Gnomad SAS AF: 0.101

Gnomad FIN AF: 0.0405

Gnomad MID AF: 0.171

Gnomad NFE AF: 0.0837

Gnomad OTH AF: 0.115

GnomAD4 exome AF: 0.0845 AC: 36384 AN: 430560 Hom.: 1823 Cov.: 6 AF XY: 0.0874 AC XY: 20331 AN XY: 232708

Gnomad4 AFR exome AF: 0.114

Gnomad4 AMR exome AF: 0.0693

Gnomad4 ASJ exome AF: 0.144

Gnomad4 EAS exome AF: 0.0150

Gnomad4 SAS exome AF: 0.110

Gnomad4 FIN exome AF: 0.0492

Gnomad4 NFE exome AF: 0.0839

Gnomad4 OTH exome AF: 0.0914

GnomAD4 genome AF: 0.0928 AC: 14121 AN: 152242 Hom.: 720 Cov.: 32 AF XY: 0.0912 AC XY: 6788 AN XY: 74454

Gnomad4 AFR AF: 0.119

Gnomad4 AMR AF: 0.0862

Gnomad4 ASJ AF: 0.156

Gnomad4 EAS AF: 0.0204

Gnomad4 SAS AF: 0.101

Gnomad4 FIN AF: 0.0405

Gnomad4 NFE AF: 0.0837

Gnomad4 OTH AF: 0.115

Alfa AF: 0.0906 Hom.: 271

Bravo AF: 0.0979

Asia WGS AF: 0.0580 AC: 203 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.2
DANN	Benign	0.65

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: rs12825616; hg19: chr12-19472835;