rs1383213719

Variant names:

• chr6-150733694-G-A
• rs1383213719
• NM_001029884.3:c.13G>A

Your query was ambiguous. Multiple possible variants found:

• chr6-150733694-G-A
• chr6-150733694-G-C

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001029884.3(PLEKHG1):​c.13G>A​(p.Asp5Asn) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 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: 4.40
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.32203192).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLEKHG1	NM_001029884.3	c.13G>A	p.Asp5Asn	missense_variant	Exon 3 of 17	ENST00000696526.1	NP_001025055.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLEKHG1	ENST00000696526.1	c.13G>A	p.Asp5Asn	missense_variant	Exon 3 of 17		NM_001029884.3	ENSP00000512689.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Aug 22, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.13G>A (p.D5N) alteration is located in exon 3 (coding exon 1) of the PLEKHG1 gene. This alteration results from a G to A substitution at nucleotide position 13, causing the aspartic acid (D) at amino acid position 5 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.25
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Pathogenic	26
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.052	.;T;.;T
Eigen	Pathogenic	0.74
Eigen_PC	Pathogenic	0.73
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Uncertain	0.93	D;.;D;D
M_CAP	Benign	0.033	D
MetaRNN	Benign	0.32	T;T;T;T
MetaSVM	Benign	-0.38	T
MutationAssessor	Uncertain	2.2	.;M;.;M
PhyloP100		4.4
PrimateAI	Uncertain	0.72	T
PROVEAN	Pathogenic	-5.0	D;.;.;N
REVEL	Benign	0.23
Sift	Uncertain	0.0030	.;.;.;D
Sift4G	Pathogenic	0.0	D;.;.;T
Polyphen		1.0	.;D;.;D
Vest4		0.59
MutPred		0.11		Gain of sheet (P = 0.1945);Gain of sheet (P = 0.1945);.;Gain of sheet (P = 0.1945);
MVP		0.86
ClinPred		0.86	D
GERP RS		5.7
Varity_R		0.11
gMVP		0.49
Mutation Taster		=88/12	polymorphism

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: rs1383213719; hg19: chr6-151054830; COSMIC: COSV62049173; COSMIC: COSV62049173;