rs200045272

Variant names:

• chr6-150733983-C-A
• rs200045272
• NM_001029884.3:c.302C>A

Your query was ambiguous. Multiple possible variants found:

• chr6-150733983-C-A
• chr6-150733983-C-T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_001029884.3(PLEKHG1):​c.302C>A​(p.Thr101Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00015 in 1,614,156 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T101M) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000046 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00016 (0 hom.)
• Consequence: PLEKHG1 NM_001029884.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.242
• Publications: 3 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: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.040549964).
• BS2: High AC in GnomAd4 at 7 AD gene.

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.302C>A	p.Thr101Lys	missense	Exon 3 of 17	NP_001025055.1	Q9ULL1
	PLEKHG1	NM_001329798.2		c.479C>A	p.Thr160Lys	missense	Exon 2 of 16	NP_001316727.1
	PLEKHG1	NM_001329799.2		c.422C>A	p.Thr141Lys	missense	Exon 2 of 16	NP_001316728.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLEKHG1	ENST00000696526.1	MANE Select	c.302C>A	p.Thr101Lys	missense	Exon 3 of 17	ENSP00000512689.1	Q9ULL1
	PLEKHG1	ENST00000358517.6	TSL:5	c.302C>A	p.Thr101Lys	missense	Exon 2 of 16	ENSP00000351318.2	Q9ULL1
	PLEKHG1	ENST00000644968.1		c.302C>A	p.Thr101Lys	missense	Exon 2 of 16	ENSP00000496254.1	Q9ULL1

Frequencies

GnomAD3 genomes AF: 0.0000460 AC: 7 AN: 152176 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000724

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0000942

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000111 AC: 28 AN: 251226 AF XY: 0.000140

Gnomad AFR exome AF: 0.0000617

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000462

Gnomad NFE exome AF: 0.000229

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000161 AC: 235 AN: 1461862 Hom.: 0 Cov.: 32 AF XY: 0.000143 AC XY: 104 AN XY: 727230

African (AFR) AF: 0.0000299 AC: 1 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.0000936 AC: 5 AN: 53398

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.000201 AC: 223 AN: 1112002

Other (OTH) AF: 0.0000993 AC: 6 AN: 60396

GnomAD4 genome AF: 0.0000460 AC: 7 AN: 152294 Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2 AN XY: 74456

African (AFR) AF: 0.0000722 AC: 3 AN: 41560

American (AMR) AF: 0.00 AC: 0 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.00 AC: 0 AN: 4820

European-Finnish (FIN) AF: 0.0000942 AC: 1 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 68026

Other (OTH) AF: 0.00 AC: 0 AN: 2112

Alfa AF: 0.000127 Hom.: 0

Bravo AF: 0.0000680

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000519 AC: 2

ExAC AF: 0.000214 AC: 26

EpiCase AF: 0.00

EpiControl AF: 0.000178

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	-0.42	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	4.8
DANN	Benign	0.67
DEOGEN2	Benign	0.0035	T
Eigen	Benign	-0.97
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.056	N
LIST_S2	Benign	0.59	T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.041	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.8	L
PhyloP100		0.24
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-0.93	N
REVEL	Benign	0.035
Sift	Benign	0.031	D
Sift4G	Benign	0.58	T
Polyphen		0.39	B
Vest4		0.22
MVP		0.67
ClinPred		0.027	T
GERP RS		1.6
Varity_R		0.048
gMVP		0.21
Mutation Taster		=97/3	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: rs200045272; hg19: chr6-151055119;