6-150705265-T-A

Variant names:

• chr6-150705265-T-A
• rs6940976
• NM_001029884.3:c.-98-28319T>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001029884.3(PLEKHG1):​c.-98-28319T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 34)
• Consequence: PLEKHG1 NM_001029884.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.845
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001029884.3. 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
	PLEKHG1	NM_001029884.3	MANE Select	c.-98-28319T>A		intron	N/A	NP_001025055.1
	PLEKHG1	NM_001329798.2		c.79+21424T>A		intron	N/A	NP_001316727.1
	PLEKHG1	NM_001329799.2		c.23-28319T>A		intron	N/A	NP_001316728.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLEKHG1	ENST00000696526.1	MANE Select	c.-98-28319T>A		intron	N/A	ENSP00000512689.1
	PLEKHG1	ENST00000644968.1		c.-99+21383T>A		intron	N/A	ENSP00000496254.1
	PLEKHG1	ENST00000644913.1		c.118+18275T>A		intron	N/A	ENSP00000493494.1

Frequencies

GnomAD3 genomes Cov.: 34

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

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	8.7
DANN	Benign	0.73
PhyloP100		0.84

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: rs6940976; hg19: chr6-151026401;