Genetic Variant PLEKHA6:p.Gly6Gly (chr1-204273710-A-C) – ACMG Classification: Benign (-11 pts)

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_ModerateBP7BA1

The NM_014935.5(PLEKHA6):c.18T>G(p.Gly6Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.176 in 1,612,072 control chromosomes in the GnomAD database, including 26,090 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 0.18 ( 2522 hom., cov: 32)

Exomes 𝑓: 0.18 ( 23568 hom. )

Consequence

PLEKHA6
NM_014935.5 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.260

Publications

15 publications found

Variant links:

Genes affected

PLEKHA6 (HGNC:17053): (pleckstrin homology domain containing A6)

PLEKHA6 Gene-Disease associations (from GenCC):

schizophrenia
Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

PLEKHA6 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.46).

BP7

Synonymous conserved (PhyloP=0.26 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.271 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLEKHA6	NM_014935.5 link	c.18T>G	p.Gly6Gly	synonymous_variant	Exon 3 of 23	ENST00000272203.8	NP_055750.2	Q9Y2H5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLEKHA6	ENST00000272203.8 link	c.18T>G	p.Gly6Gly	synonymous_variant	Exon 3 of 23	1	NM_014935.5	ENSP00000272203.2		Q9Y2H5

Frequencies

GnomAD3 genomes

AF:

0.178

AC:

27062

AN:

151726

Hom.:

2520

Cov.:

show subpopulations

Gnomad AFR

AF:

0.142

Gnomad AMI

AF:

0.122

Gnomad AMR

AF:

0.212

Gnomad ASJ

AF:

0.141

Gnomad EAS

AF:

0.283

Gnomad SAS

AF:

0.198

Gnomad FIN

AF:

0.251

Gnomad MID

AF:

0.101

Gnomad NFE

AF:

0.176

Gnomad OTH

AF:

0.170

GnomAD2 exomes

AF:

0.193

AC:

48375

AN:

251220

AF XY:

0.190

show subpopulations

Gnomad AFR exome

AF:

0.140

Gnomad AMR exome

AF:

0.243

Gnomad ASJ exome

AF:

0.136

Gnomad EAS exome

AF:

0.274

Gnomad FIN exome

AF:

0.245

Gnomad NFE exome

AF:

0.171

Gnomad OTH exome

AF:

0.170

GnomAD4 exome

AF:

0.176

AC:

256808

AN:

1460228

Hom.:

23568

Cov.:

AF XY:

0.176

AC XY:

127830

AN XY:

726526

show subpopulations

African (AFR)

AF:

0.133

AC:

4454

AN:

33460

American (AMR)

AF:

0.238

AC:

10622

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.139

AC:

3626

AN:

26122

East Asian (EAS)

AF:

0.259

AC:

10291

AN:

39684

South Asian (SAS)

AF:

0.182

AC:

15733

AN:

86228

European-Finnish (FIN)

AF:

0.241

AC:

12893

AN:

53404

Middle Eastern (MID)

AF:

0.138

AC:

798

AN:

5766

European-Non Finnish (NFE)

AF:

0.169

AC:

187581

AN:

1110506

Other (OTH)

AF:

0.179

AC:

10810

AN:

60340

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.464

Heterozygous variant carriers

9573

19146

28720

38293

47866

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

6622

13244

19866

26488

33110

<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:

0.178

AC:

27079

AN:

151844

Hom.:

2522

Cov.:

AF XY:

0.184

AC XY:

13659

AN XY:

74200

show subpopulations

African (AFR)

AF:

0.141

AC:

5856

AN:

41392

American (AMR)

AF:

0.212

AC:

3242

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.141

AC:

490

AN:

3468

East Asian (EAS)

AF:

0.283

AC:

1453

AN:

5138

South Asian (SAS)

AF:

0.197

AC:

949

AN:

4810

European-Finnish (FIN)

AF:

0.251

AC:

2647

AN:

10534

Middle Eastern (MID)

AF:

0.0952

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.176

AC:

11946

AN:

67924

Other (OTH)

AF:

0.170

AC:

357

AN:

2098

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1127

2254

3380

4507

5634

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

306

612

918

1224

1530

<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:

0.168

Hom.:

2531

Bravo

AF:

0.172

Asia WGS

AF:

0.273

AC:

950

AN:

3478

EpiCase

AF:

0.165

EpiControl

AF:

0.166

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.46

CADD

Benign

(source)

DANN

Benign

0.77

PhyloP100

0.26

Mutation Taster

=100/0

polymorphism (auto)

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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