Genetic Variant PLEKHG6:c.*217A>G (chr12-6328362-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.280

Publications

4 publications found

Variant links:

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]

PLEKHG6 links:

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ACMG classification

Classification was made for transcript

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLEKHG6	NM_001384598.1 link	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 link	c.*217A>G		3_prime_UTR_variant	Exon 16 of 16		NM_001384598.1	ENSP00000506982.1		Q3KR16-1

Frequencies

GnomAD3 genomes

AF:

0.0163

AC:

2486

AN:

152194

Hom.:

Cov.:

show subpopulations

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.:

Cov.:

AF XY:

0.00183

AC XY:

360

AN XY:

196268

show subpopulations

African (AFR)

AF:

0.0579

AC:

591

AN:

10206

American (AMR)

AF:

0.00423

AC:

AN:

13956

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

11936

East Asian (EAS)

AF:

0.00

AC:

AN:

26066

South Asian (SAS)

AF:

0.000281

AC:

AN:

31976

European-Finnish (FIN)

AF:

0.00

AC:

AN:

26602

Middle Eastern (MID)

AF:

0.00267

AC:

AN:

2620

European-Non Finnish (NFE)

AF:

0.000113

AC:

AN:

229412

Other (OTH)

AF:

0.00477

AC:

107

AN:

22414

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.518

Heterozygous variant carriers

109

146

182

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0163

AC:

2488

AN:

152312

Hom.:

Cov.:

AF XY:

0.0163

AC XY:

1214

AN XY:

74476

show subpopulations

African (AFR)

AF:

0.0566

AC:

2354

AN:

41562

American (AMR)

AF:

0.00647

AC:

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5176

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000176

AC:

AN:

68034

Other (OTH)

AF:

0.0104

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

124

248

371

495

619

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

104

130

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00628

Hom.:

Bravo

AF:

0.0179

Asia WGS

AF:

0.00202

AC:

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

(source)

DANN

Benign

0.90

PhyloP100

0.28

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Mutation Taster

=100/0

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over