12-6313168-TG-T

Position:

• chr12-6313168-TG-T

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_Moderate BS2

The NM_001384598.1(PLEKHG6):​c.139-457del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000663 in 1,550,118 control chromosomes in the GnomAD database, including 14 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.00056 (2 hom., cov: 34)
  • Exomes 𝑓: 0.00067 (12 hom.)
• Consequence: PLEKHG6 NM_001384598.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0620

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 Likely_benign. Variant got -6 ACMG points.

• BP6: Variant 12-6313168-TG-T is Benign according to our data. Variant chr12-6313168-TG-T is described in ClinVar as [Benign]. Clinvar id is 3038576.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PLEKHG6	NM_001384598.1	c.139-457del		intron_variant		ENST00000684764.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PLEKHG6	ENST00000684764.1	c.139-457del		intron_variant			NM_001384598.1	P1

Frequencies

GnomAD3 genomes AF: 0.000526 AC: 80 AN: 152184 Hom.: 2 Cov.: 34

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000458

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0132

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00239

GnomAD3 exomes AF: 0.00161 AC: 247 AN: 153448 Hom.: 1 AF XY: 0.00219 AC XY: 179 AN XY: 81584

Gnomad AFR exome AF: 0.000127

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000919

Gnomad SAS exome AF: 0.0105

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000169

Gnomad OTH exome AF: 0.00139

GnomAD4 exome AF: 0.000674 AC: 942 AN: 1397816 Hom.: 12 Cov.: 34 AF XY: 0.000939 AC XY: 647 AN XY: 689224

Gnomad4 AFR exome AF: 0.0000317

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000841

Gnomad4 SAS exome AF: 0.0104

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000362

Gnomad4 OTH exome AF: 0.00123

GnomAD4 genome AF: 0.000558 AC: 85 AN: 152302 Hom.: 2 Cov.: 34 AF XY: 0.000698 AC XY: 52 AN XY: 74482

Gnomad4 AFR AF: 0.0000241

Gnomad4 AMR AF: 0.000457

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.0133

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000294

Gnomad4 OTH AF: 0.00473

Alfa AF: 0.000260 Hom.: 0

Bravo AF: 0.000174

Asia WGS AF: 0.0240 AC: 84 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

PLEKHG6-related disorder Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Apr 06, 2022

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs540989527; hg19: chr12-6422334;