14-64709851-A-G

Variant names:

• chr14-64709851-A-G
• rs732311
• NM_001308147.2:c.-40+5147A>G

Variant summary

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

The NM_001308147.2(PLEKHG3):​c.-40+5147A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0855 in 152,026 control chromosomes in the GnomAD database, including 606 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 0.086 (606 hom., cov: 31)
• Consequence: PLEKHG3 NM_001308147.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00600
• Publications: 3 publications found

Genes affected

PLEKHG3 (HGNC:20364): (pleckstrin homology and RhoGEF domain containing G3) Predicted to enable guanyl-nucleotide exchange factor activity. Predicted to be involved in regulation of small GTPase mediated signal transduction. Predicted to be located in cytosol. [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=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.109 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001308147.2. 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
	PLEKHG3	NM_001308147.2	MANE Select	c.-40+5147A>G		intron	N/A	NP_001295076.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLEKHG3	ENST00000247226.13	TSL:1 MANE Select	c.-40+5147A>G		intron	N/A	ENSP00000247226.8
	PLEKHG3	ENST00000394691.7	TSL:5	c.-40+5147A>G		intron	N/A	ENSP00000378183.2
	PLEKHG3	ENST00000555982.5	TSL:3	c.-40+5720A>G		intron	N/A	ENSP00000450501.1

Frequencies

GnomAD3 genomes AF: 0.0856 AC: 12996 AN: 151908 Hom.: 607 Cov.: 31

Gnomad AFR AF: 0.111

Gnomad AMI AF: 0.0736

Gnomad AMR AF: 0.0706

Gnomad ASJ AF: 0.0860

Gnomad EAS AF: 0.00444

Gnomad SAS AF: 0.0762

Gnomad FIN AF: 0.0501

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.0858

Gnomad OTH AF: 0.0854

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

GnomAD4 genome AF: 0.0855 AC: 13004 AN: 152026 Hom.: 606 Cov.: 31 AF XY: 0.0837 AC XY: 6220 AN XY: 74306

African (AFR) AF: 0.111 AC: 4612 AN: 41448

American (AMR) AF: 0.0705 AC: 1077 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.0860 AC: 298 AN: 3466

East Asian (EAS) AF: 0.00445 AC: 23 AN: 5172

South Asian (SAS) AF: 0.0773 AC: 372 AN: 4812

European-Finnish (FIN) AF: 0.0501 AC: 529 AN: 10568

Middle Eastern (MID) AF: 0.0544 AC: 16 AN: 294

European-Non Finnish (NFE) AF: 0.0858 AC: 5832 AN: 67974

Other (OTH) AF: 0.0845 AC: 178 AN: 2106

Alfa AF: 0.0866 Hom.: 325

Bravo AF: 0.0866

Asia WGS AF: 0.0520 AC: 181 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	3.2
DANN	Benign	0.73
PhyloP100		0.0060
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: rs732311; hg19: chr14-65176569;