chr12-19375704-G-A

Position:

• chr12-19375704-G-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_001256470.2(PLEKHA5):​c.*185G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0757 in 152,372 control chromosomes in the GnomAD database, including 526 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 0.076 (522 hom., cov: 32)
  • Exomes 𝑓: 0.086 (4 hom.)
• Consequence: PLEKHA5 NM_001256470.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.49

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.37).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.115 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PLEKHA5	NM_001256470.2	c.*185G>A		3_prime_UTR_variant	32/32	ENST00000429027.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PLEKHA5	ENST00000429027.7	c.*185G>A		3_prime_UTR_variant	32/32	1	NM_001256470.2	A2

Frequencies

GnomAD3 genomes AF: 0.0756 AC: 11485 AN: 151826 Hom.: 518 Cov.: 32

Gnomad AFR AF: 0.0200

Gnomad AMI AF: 0.0296

Gnomad AMR AF: 0.0893

Gnomad ASJ AF: 0.101

Gnomad EAS AF: 0.0845

Gnomad SAS AF: 0.123

Gnomad FIN AF: 0.0859

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.0998

Gnomad OTH AF: 0.0834

GnomAD4 exome AF: 0.0864 AC: 37 AN: 428 Hom.: 4 Cov.: 0 AF XY: 0.0742 AC XY: 19 AN XY: 256

Gnomad4 FIN exome AF: 0.0877

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0757 AC: 11504 AN: 151944 Hom.: 522 Cov.: 32 AF XY: 0.0764 AC XY: 5676 AN XY: 74264

Gnomad4 AFR AF: 0.0200

Gnomad4 AMR AF: 0.0899

Gnomad4 ASJ AF: 0.101

Gnomad4 EAS AF: 0.0847

Gnomad4 SAS AF: 0.124

Gnomad4 FIN AF: 0.0859

Gnomad4 NFE AF: 0.0997

Gnomad4 OTH AF: 0.0859

Alfa AF: 0.0963 Hom.: 946

Bravo AF: 0.0729

Asia WGS AF: 0.112 AC: 393 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.37
CADD	Benign	14
DANN	Benign	0.87

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: rs3752823; hg19: chr12-19528638;