rs9397339

Variant names:

• chr6-150615356-A-G
• rs9397339
• NM_001029884.3:c.-158+15339A>G

Variant summary

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

The NM_001029884.3(PLEKHG1):​c.-158+15339A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0444 in 152,214 control chromosomes in the GnomAD database, including 354 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 0.044 (354 hom., cov: 32)
• Consequence: PLEKHG1 NM_001029884.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.323
• Publications: 1 publications found

Genes affected

PLEKHG1 (HGNC:20884): (pleckstrin homology and RhoGEF domain containing G1) Predicted to enable guanyl-nucleotide exchange factor activity. Predicted to be involved in regulation of small GTPase mediated signal transduction. Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

PLEKHG1 Gene-Disease associations (from GenCC):

• periventricular leukomalacia

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.108 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLEKHG1	NM_001029884.3	c.-158+15339A>G		intron_variant	Intron 1 of 16	ENST00000696526.1	NP_001025055.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLEKHG1	ENST00000696526.1	c.-158+15339A>G		intron_variant	Intron 1 of 16		NM_001029884.3	ENSP00000512689.1
PLEKHG1	ENST00000367326.1	c.-204+15339A>G		intron_variant	Intron 1 of 3	3		ENSP00000356295.1
PLEKHG1	ENST00000643446.1	n.115+15339A>G		intron_variant	Intron 1 of 2
PLEKHG1	ENST00000643692.1	n.115+15339A>G		intron_variant	Intron 1 of 2

Frequencies

GnomAD3 genomes AF: 0.0443 AC: 6731 AN: 152096 Hom.: 344 Cov.: 32

Gnomad AFR AF: 0.111

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.101

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.0718

Gnomad SAS AF: 0.0160

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000823

Gnomad OTH AF: 0.0368

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

GnomAD4 genome AF: 0.0444 AC: 6762 AN: 152214 Hom.: 354 Cov.: 32 AF XY: 0.0451 AC XY: 3357 AN XY: 74426

African (AFR) AF: 0.111 AC: 4613 AN: 41502

American (AMR) AF: 0.102 AC: 1563 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3472

East Asian (EAS) AF: 0.0718 AC: 372 AN: 5180

South Asian (SAS) AF: 0.0162 AC: 78 AN: 4816

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10610

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.000823 AC: 56 AN: 68032

Other (OTH) AF: 0.0364 AC: 77 AN: 2116

Alfa AF: 0.0471 Hom.: 92

Bravo AF: 0.0556

Asia WGS AF: 0.0440 AC: 153 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.8
DANN	Benign	0.71
PhyloP100		-0.32
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: rs9397339; hg19: chr6-150936492;