rs4149650

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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

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 Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLEKHG6	NM_001384598.1	c.*217A>G		3_prime_UTR_variant	Exon 16 of 16	ENST00000684764.1	NP_001371527.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLEKHG6	ENST00000684764.1	c.*217A>G		3_prime_UTR_variant	Exon 16 of 16		NM_001384598.1	ENSP00000506982.1

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

Gnomad4 AFR exome AF: 0.0579

Gnomad4 AMR exome AF: 0.00423

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000281

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000113

Gnomad4 OTH exome AF: 0.00477

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

Gnomad4 AFR AF: 0.0566

Gnomad4 AMR AF: 0.00647

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000176

Gnomad4 OTH AF: 0.0104

Alfa AF: 0.00374 Hom.: 5

Bravo AF: 0.0179

Asia WGS AF: 0.00202 AC: 7 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
CADD	Benign	3.0
DANN	Benign	0.90
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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

Publications

LitVar

Other links and lift over

dbSNP: rs4149650; hg19: chr12-6437528;