chr12-6324123-C-G

Variant names:

• chr12-6324123-C-G
• rs740841
• NM_001384598.1:c.1525-2305C>G

Variant summary

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

The NM_001384598.1(PLEKHG6):​c.1525-2305C>G 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: 31)
• Consequence: PLEKHG6 NM_001384598.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.203
• Publications: 6 publications found

Genes affected

PLEKHG6 (HGNC:25562): (pleckstrin homology and RhoGEF domain containing G6) Predicted to enable guanyl-nucleotide exchange factor activity. Predicted to be involved in regulation of small GTPase mediated signal transduction. Located in cell junction and centrosome. [provided by Alliance of Genome Resources, Apr 2022]

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=-0.79).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001384598.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLEKHG6	NM_001384598.1	MANE Select	c.1525-2305C>G		intron	N/A	NP_001371527.1	Q3KR16-1
	PLEKHG6	NM_001384604.1		c.1573-2305C>G		intron	N/A	NP_001371533.1
	PLEKHG6	NM_001144856.2		c.1525-2305C>G		intron	N/A	NP_001138328.1	A0A2X0TW08

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLEKHG6	ENST00000684764.1	MANE Select	c.1525-2305C>G		intron	N/A	ENSP00000506982.1	Q3KR16-1
	PLEKHG6	ENST00000011684.11	TSL:1	c.1525-2305C>G		intron	N/A	ENSP00000011684.7	Q3KR16-1
	PLEKHG6	ENST00000304581.8	TSL:1	c.115-2305C>G		intron	N/A	ENSP00000304640.8	Q3KR16-3

Frequencies

GnomAD3 genomes Cov.: 31

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

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 7374

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	3.8
DANN	Benign	0.69
PhyloP100		0.20

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: rs740841; hg19: chr12-6433289;