rs1468603

chr12-6317886-C-Gchr12-6317886-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 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. 12/21 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

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PLEKHG6	NM_001384598.1	c.1047C>G	p.His349Gln	missense_variant	10/16	ENST00000684764.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PLEKHG6	ENST00000684764.1	c.1047C>G	p.His349Gln	missense_variant	10/16		NM_001384598.1	P1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 48

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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;.;T;.
Eigen	Benign	-0.046
Eigen_PC	Benign	0.029
FATHMM_MKL	Uncertain	0.88	D
M_CAP	Benign	0.059	D
MetaRNN	Benign	0.22	T;T;T;T
MetaSVM	Benign	-0.42	T
MutationAssessor	Benign	1.6	L;.;L;.
MutationTaster	Benign	0.92	P;P;P;P
PrimateAI	Uncertain	0.50	T
PROVEAN	Uncertain	-2.9	D;D;D;D
REVEL	Benign	0.10
Sift	Benign	0.14	T;T;T;T
Sift4G	Uncertain	0.013	D;D;D;D
Polyphen		0.90	P;B;P;B
Vest4		0.39
MutPred		0.47		Gain of disorder (P = 0.0352);Gain of disorder (P = 0.0352);Gain of disorder (P = 0.0352);.;
MVP		0.47
MPC		0.16
ClinPred		0.34	T
GERP RS		3.8
Varity_R		0.22
gMVP		0.28

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

Publications

LitVar

Other links and lift over

dbSNP: rs1468603; hg19: chr12-6427052;