chr12-19316144-A-G

Variant names:

• chr12-19316144-A-G
• rs10743315
• NM_001256470.2:c.2118+1250A>G

Variant summary

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

The NM_001256470.2(PLEKHA5):​c.2118+1250A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.723 in 151,804 control chromosomes in the GnomAD database, including 42,035 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 0.72 (42035 hom., cov: 29)
• Consequence: PLEKHA5 NM_001256470.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.403
• Publications: 11 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 = 0.856 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001256470.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLEKHA5	NM_001256470.2	MANE Select	c.2118+1250A>G		intron	N/A	NP_001243399.1
	PLEKHA5	NM_001385923.1		c.2100+1250A>G		intron	N/A	NP_001372852.1
	PLEKHA5	NM_001385924.1		c.2118+1250A>G		intron	N/A	NP_001372853.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLEKHA5	ENST00000429027.7	TSL:1 MANE Select	c.2118+1250A>G		intron	N/A	ENSP00000404296.2
	PLEKHA5	ENST00000538714.5	TSL:1	c.2020-4418A>G		intron	N/A	ENSP00000439673.1
	PLEKHA5	ENST00000299275.10	TSL:1	c.1846-4418A>G		intron	N/A	ENSP00000299275.6

Frequencies

GnomAD3 genomes AF: 0.723 AC: 109727 AN: 151686 Hom.: 42052 Cov.: 29

Gnomad AFR AF: 0.479

Gnomad AMI AF: 0.969

Gnomad AMR AF: 0.776

Gnomad ASJ AF: 0.829

Gnomad EAS AF: 0.399

Gnomad SAS AF: 0.663

Gnomad FIN AF: 0.833

Gnomad MID AF: 0.842

Gnomad NFE AF: 0.862

Gnomad OTH AF: 0.758

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

GnomAD4 genome AF: 0.723 AC: 109721 AN: 151804 Hom.: 42035 Cov.: 29 AF XY: 0.719 AC XY: 53316 AN XY: 74198

African (AFR) AF: 0.478 AC: 19782 AN: 41372

American (AMR) AF: 0.775 AC: 11795 AN: 15216

Ashkenazi Jewish (ASJ) AF: 0.829 AC: 2878 AN: 3472

East Asian (EAS) AF: 0.398 AC: 2051 AN: 5154

South Asian (SAS) AF: 0.663 AC: 3180 AN: 4794

European-Finnish (FIN) AF: 0.833 AC: 8792 AN: 10558

Middle Eastern (MID) AF: 0.833 AC: 245 AN: 294

European-Non Finnish (NFE) AF: 0.862 AC: 58537 AN: 67926

Other (OTH) AF: 0.749 AC: 1579 AN: 2108

Alfa AF: 0.819 Hom.: 25564

Bravo AF: 0.710

Asia WGS AF: 0.482 AC: 1678 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.98
DANN	Benign	0.61
PhyloP100		-0.40
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: rs10743315; hg19: chr12-19469078;