Genetic Variant PLEKHA5:c.227+18388T>C (chr12-19150838-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_001256470.2(PLEKHA5):c.227+18388T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.668 in 152,054 control chromosomes in the GnomAD database, including 37,319 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 0.67 ( 37313 hom., cov: 31)

Exomes 𝑓: 0.61 ( 6 hom. )

Consequence

PLEKHA5
NM_001256470.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.269

Publications

6 publications found

Variant links:

Genes affected

PLEKHA5 (HGNC:30036): (pleckstrin homology domain containing A5) Predicted to enable phosphatidylinositol phosphate binding activity. Predicted to act upstream of or within reproductive system development. Located in cytosol and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

PLEKHA5 links:

ENSG00000253284 (HGNC:):

ENSG00000253284 links:

Genome browser will be placed here

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=-0.88).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.828 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001256470.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
PLEKHA5	NM_001256470.2	MANE Select	c.227+18388T>C	intron	N/A	NP_001243399.1	Q9HAU0-6
PLEKHA5	NM_001385923.1		c.227+18388T>C	intron	N/A	NP_001372852.1
PLEKHA5	NM_001385924.1		c.227+18388T>C	intron	N/A	NP_001372853.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
PLEKHA5	ENST00000429027.7	TSL:1 MANE Select	c.227+18388T>C	intron	N/A	ENSP00000404296.2	Q9HAU0-6
PLEKHA5	ENST00000538714.5	TSL:1	c.227+18388T>C	intron	N/A	ENSP00000439673.1	Q9HAU0-2
PLEKHA5	ENST00000299275.10	TSL:1	c.227+18388T>C	intron	N/A	ENSP00000299275.6	Q9HAU0-1

Frequencies

GnomAD3 genomes

AF:

0.669

AC:

101579

AN:

151908

Hom.:

37320

Cov.:

show subpopulations

Gnomad AFR

AF:

0.345

Gnomad AMI

AF:

0.658

Gnomad AMR

AF:

0.656

Gnomad ASJ

AF:

0.728

Gnomad EAS

AF:

0.650

Gnomad SAS

AF:

0.741

Gnomad FIN

AF:

0.836

Gnomad MID

AF:

0.674

Gnomad NFE

AF:

0.834

Gnomad OTH

AF:

0.702

GnomAD4 exome

AF:

0.607

AC:

AN:

Hom.:

Cov.:

AF XY:

0.500

AC XY:

AN XY:

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.500

AC:

AN:

East Asian (EAS)

AF:

0.500

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.500

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.700

AC:

AN:

Other (OTH)

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

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:

0.668

AC:

101603

AN:

152026

Hom.:

37313

Cov.:

AF XY:

0.666

AC XY:

49512

AN XY:

74334

show subpopulations

African (AFR)

AF:

0.345

AC:

14290

AN:

41412

American (AMR)

AF:

0.656

AC:

10033

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.728

AC:

2525

AN:

3468

East Asian (EAS)

AF:

0.649

AC:

3340

AN:

5146

South Asian (SAS)

AF:

0.742

AC:

3570

AN:

4812

European-Finnish (FIN)

AF:

0.836

AC:

8860

AN:

10594

Middle Eastern (MID)

AF:

0.670

AC:

197

AN:

294

European-Non Finnish (NFE)

AF:

0.834

AC:

56711

AN:

67996

Other (OTH)

AF:

0.701

AC:

1477

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1388

2775

4163

5550

6938

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

788

1576

2364

3152

3940

<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:

0.765

Hom.:

120276

Bravo

AF:

0.641

Asia WGS

AF:

0.654

AC:

2275

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

4.9

(source)

DANN

Benign

0.84

PhyloP100

0.27

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over