NM_001308147.2:c.-40+6493G>A

Variant names:

• chr14-64711197-G-A
• rs12895353
• NM_001308147.2:c.-40+6493G>A

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+6493G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0682 in 152,162 control chromosomes in the GnomAD database, including 396 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 0.068 (396 hom., cov: 32)
• Consequence: PLEKHG3 NM_001308147.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0250
• Publications: 1 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=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0835 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLEKHG3	NM_001308147.2	c.-40+6493G>A		intron_variant	Intron 1 of 16	ENST00000247226.13	NP_001295076.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLEKHG3	ENST00000247226.13	c.-40+6493G>A		intron_variant	Intron 1 of 16	1	NM_001308147.2	ENSP00000247226.8
PLEKHG3	ENST00000394691.7	c.-40+6493G>A		intron_variant	Intron 1 of 14	5		ENSP00000378183.2
PLEKHG3	ENST00000555982.5	c.-40+7066G>A		intron_variant	Intron 1 of 4	3		ENSP00000450501.1

Frequencies

GnomAD3 genomes AF: 0.0683 AC: 10380 AN: 152042 Hom.: 397 Cov.: 32

Gnomad AFR AF: 0.0513

Gnomad AMI AF: 0.0735

Gnomad AMR AF: 0.0654

Gnomad ASJ AF: 0.0874

Gnomad EAS AF: 0.00443

Gnomad SAS AF: 0.0760

Gnomad FIN AF: 0.0502

Gnomad MID AF: 0.0545

Gnomad NFE AF: 0.0854

Gnomad OTH AF: 0.0703

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

GnomAD4 genome AF: 0.0682 AC: 10379 AN: 152162 Hom.: 396 Cov.: 32 AF XY: 0.0670 AC XY: 4981 AN XY: 74392

African (AFR) AF: 0.0511 AC: 2120 AN: 41502

American (AMR) AF: 0.0653 AC: 998 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0874 AC: 303 AN: 3468

East Asian (EAS) AF: 0.00444 AC: 23 AN: 5184

South Asian (SAS) AF: 0.0771 AC: 371 AN: 4812

European-Finnish (FIN) AF: 0.0502 AC: 532 AN: 10590

Middle Eastern (MID) AF: 0.0514 AC: 15 AN: 292

European-Non Finnish (NFE) AF: 0.0853 AC: 5803 AN: 68000

Other (OTH) AF: 0.0695 AC: 147 AN: 2114

Alfa AF: 0.0817 Hom.: 276

Bravo AF: 0.0663

Asia WGS AF: 0.0510 AC: 177 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	2.5
DANN	Benign	0.76
PhyloP100		-0.025
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: rs12895353; hg19: chr14-65177915;