rs1468603

Variant names:

• chr12-6317886-C-G
• rs1468603
• NM_001384598.1:c.1047C>G
• PLEKHG6 p.His349Gln

Your query was ambiguous. Multiple possible variants found:

• chr12-6317886-C-G
• chr12-6317886-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001384598.1(PLEKHG6):​c.1047C>G​(p.His349Gln) variant causes a missense 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. 13/22 in silico tools predict 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: PLEKHG6 NM_001384598.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.17
• Publications: 18 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.21537268).

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.1047C>G	p.His349Gln	missense	Exon 10 of 16	NP_001371527.1	Q3KR16-1
	PLEKHG6	NM_001384604.1		c.1095C>G	p.His365Gln	missense	Exon 10 of 16	NP_001371533.1
	PLEKHG6	NM_001144856.2		c.1047C>G	p.His349Gln	missense	Exon 10 of 16	NP_001138328.1	A0A2X0TW08

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLEKHG6	ENST00000684764.1	MANE Select	c.1047C>G	p.His349Gln	missense	Exon 10 of 16	ENSP00000506982.1	Q3KR16-1
	PLEKHG6	ENST00000011684.11	TSL:1	c.1047C>G	p.His349Gln	missense	Exon 10 of 16	ENSP00000011684.7	Q3KR16-1
	PLEKHG6	ENST00000536531.5	TSL:1	c.1047C>G	p.His349Gln	missense	Exon 10 of 12	ENSP00000442836.1	F5H731

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 48

GnomAD4 genome Cov.: 34

Alfa AF: 0.00 Hom.: 93612

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.063	T
BayesDel_noAF	Benign	-0.33
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.037	T
Eigen	Benign	-0.046
Eigen_PC	Benign	0.029
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Benign	0.74	T
M_CAP	Benign	0.059	D
MetaRNN	Benign	0.22	T
MetaSVM	Benign	-0.42	T
MutationAssessor	Benign	1.6	L
PhyloP100		1.2
PrimateAI	Uncertain	0.50	T
PROVEAN	Uncertain	-2.9	D
REVEL	Benign	0.10
Sift	Benign	0.14	T
Sift4G	Uncertain	0.013	D
Varity_R		0.22
gMVP		0.28
Mutation Taster		=88/12	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.12		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs1468603;

hg19: chr12-6427052;