chr12-6328362-A-G

Variant names:

• chr12-6328362-A-G
• rs4149650
• NM_001384598.1:c.*217A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001384598.1(PLEKHG6):​c.*217A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00623 in 527,500 control chromosomes in the GnomAD database, including 86 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.016 (68 hom., cov: 33)
  • Exomes 𝑓: 0.0021 (18 hom.)
• Consequence: PLEKHG6 NM_001384598.1 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.280
• Publications: 4 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.56).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0547 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001384598.1. 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
	PLEKHG6	NM_001384598.1	MANE Select	c.*217A>G		3_prime_UTR	Exon 16 of 16	NP_001371527.1	Q3KR16-1
	PLEKHG6	NM_001384604.1		c.*217A>G		3_prime_UTR	Exon 16 of 16	NP_001371533.1
	PLEKHG6	NM_001144856.2		c.*217A>G		3_prime_UTR	Exon 16 of 16	NP_001138328.1	A0A2X0TW08

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLEKHG6	ENST00000684764.1	MANE Select	c.*217A>G		3_prime_UTR	Exon 16 of 16	ENSP00000506982.1	Q3KR16-1
	PLEKHG6	ENST00000011684.11	TSL:1	c.*217A>G		3_prime_UTR	Exon 16 of 16	ENSP00000011684.7	Q3KR16-1
	PLEKHG6	ENST00000304581.8	TSL:1	c.*217A>G		3_prime_UTR	Exon 4 of 4	ENSP00000304640.8	Q3KR16-3

Frequencies

GnomAD3 genomes AF: 0.0163 AC: 2486 AN: 152194 Hom.: 68 Cov.: 33

Gnomad AFR AF: 0.0568

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00648

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000176

Gnomad OTH AF: 0.0105

GnomAD4 exome AF: 0.00213 AC: 799 AN: 375188 Hom.: 18 Cov.: 4 AF XY: 0.00183 AC XY: 360 AN XY: 196268

African (AFR) AF: 0.0579 AC: 591 AN: 10206

American (AMR) AF: 0.00423 AC: 59 AN: 13956

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 11936

East Asian (EAS) AF: 0.00 AC: 0 AN: 26066

South Asian (SAS) AF: 0.000281 AC: 9 AN: 31976

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 26602

Middle Eastern (MID) AF: 0.00267 AC: 7 AN: 2620

European-Non Finnish (NFE) AF: 0.000113 AC: 26 AN: 229412

Other (OTH) AF: 0.00477 AC: 107 AN: 22414

GnomAD4 genome AF: 0.0163 AC: 2488 AN: 152312 Hom.: 68 Cov.: 33 AF XY: 0.0163 AC XY: 1214 AN XY: 74476

African (AFR) AF: 0.0566 AC: 2354 AN: 41562

American (AMR) AF: 0.00647 AC: 99 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

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

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000176 AC: 12 AN: 68034

Other (OTH) AF: 0.0104 AC: 22 AN: 2114

Alfa AF: 0.00628 Hom.: 24

Bravo AF: 0.0179

Asia WGS AF: 0.00202 AC: 7 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
CADD	Benign	3.0
DANN	Benign	0.90
PhyloP100		0.28
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=100/0	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: rs4149650; hg19: chr12-6437528;