6-150795863-A-C

Variant names:

• chr6-150795863-A-C
• rs1786298761
• NM_001029884.3:c.590A>C

Variant summary

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

The NM_001029884.3(PLEKHG1):​c.590A>C​(p.Glu197Ala) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: PLEKHG1 NM_001029884.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.10
• Publications: 0 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLEKHG1	NM_001029884.3	MANE Select	c.590A>C	p.Glu197Ala	missense	Exon 6 of 17	NP_001025055.1	Q9ULL1
	PLEKHG1	NM_001329798.2		c.767A>C	p.Glu256Ala	missense	Exon 5 of 16	NP_001316727.1
	PLEKHG1	NM_001329799.2		c.710A>C	p.Glu237Ala	missense	Exon 5 of 16	NP_001316728.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLEKHG1	ENST00000696526.1	MANE Select	c.590A>C	p.Glu197Ala	missense	Exon 6 of 17	ENSP00000512689.1	Q9ULL1
	PLEKHG1	ENST00000475490.1	TSL:1	n.131A>C		non_coding_transcript_exon	Exon 3 of 15	ENSP00000433107.1	H0YD71
	PLEKHG1	ENST00000358517.6	TSL:5	c.590A>C	p.Glu197Ala	missense	Exon 5 of 16	ENSP00000351318.2	Q9ULL1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 25

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	0.0069	T
BayesDel_noAF	Benign	-0.23
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.066	T
Eigen	Uncertain	0.20
Eigen_PC	Uncertain	0.36
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.034	D
MetaRNN	Uncertain	0.53	D
MetaSVM	Benign	-0.77	T
MutationAssessor	Benign	1.3	L
PhyloP100		7.1
PrimateAI	Uncertain	0.66	T
PROVEAN	Pathogenic	-4.6	D
REVEL	Benign	0.27
Sift	Uncertain	0.023	D
Sift4G	Uncertain	0.043	D
Polyphen		0.26	B
Vest4		0.25
MutPred		0.65		Gain of helix (P = 0.0696)
MVP		0.84
ClinPred		0.99	D
GERP RS		5.6
Varity_R		0.42
gMVP		0.40
Mutation Taster		=51/49	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs1786298761; hg19: chr6-151116999;