rs10770448

Variant names:

• chr12-19191284-G-A
• rs10770448
• NM_001256470.2:c.227+58834G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001256470.2(PLEKHA5):​c.227+58834G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.558 in 152,056 control chromosomes in the GnomAD database, including 27,688 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 0.56 (27688 hom., cov: 32)
• Consequence: PLEKHA5 NM_001256470.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0460
• Publications: 2 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.741 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLEKHA5	NM_001256470.2	c.227+58834G>A		intron_variant	Intron 3 of 31	ENST00000429027.7	NP_001243399.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLEKHA5	ENST00000429027.7	c.227+58834G>A		intron_variant	Intron 3 of 31	1	NM_001256470.2	ENSP00000404296.2

Frequencies

GnomAD3 genomes AF: 0.559 AC: 84867 AN: 151938 Hom.: 27700 Cov.: 32

Gnomad AFR AF: 0.227

Gnomad AMI AF: 0.697

Gnomad AMR AF: 0.540

Gnomad ASJ AF: 0.653

Gnomad EAS AF: 0.348

Gnomad SAS AF: 0.488

Gnomad FIN AF: 0.760

Gnomad MID AF: 0.583

Gnomad NFE AF: 0.746

Gnomad OTH AF: 0.592

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.558 AC: 84847 AN: 152056 Hom.: 27688 Cov.: 32 AF XY: 0.553 AC XY: 41093 AN XY: 74308

African (AFR) AF: 0.226 AC: 9391 AN: 41472

American (AMR) AF: 0.539 AC: 8232 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.653 AC: 2268 AN: 3472

East Asian (EAS) AF: 0.347 AC: 1790 AN: 5152

South Asian (SAS) AF: 0.489 AC: 2353 AN: 4814

European-Finnish (FIN) AF: 0.760 AC: 8035 AN: 10570

Middle Eastern (MID) AF: 0.572 AC: 167 AN: 292

European-Non Finnish (NFE) AF: 0.746 AC: 50738 AN: 67988

Other (OTH) AF: 0.585 AC: 1237 AN: 2114

Alfa AF: 0.687 Hom.: 58089

Bravo AF: 0.530

Asia WGS AF: 0.350 AC: 1219 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.3
DANN	Benign	0.69
PhyloP100		-0.046
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10770448; hg19: chr12-19344218;