Variant 10-122424215-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_001001974.4(PLEKHA1):c.698G>C(p.Arg233Pro) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0 ( 0 hom., cov: 23)

Failed GnomAD Quality Control

Consequence

PLEKHA1
NM_001001974.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 8.19

Variant links:

Genes affected

PLEKHA1 (HGNC:14335): (pleckstrin homology domain containing A1) This gene encodes a pleckstrin homology domain-containing adapter protein. The encoded protein is localized to the plasma membrane where it specifically binds phosphatidylinositol 3,4-bisphosphate. This protein may be involved in the formation of signaling complexes in the plasma membrane. Polymorphisms in this gene are associated with age-related macular degeneration. Alternate splicing results in multiple transcript variants. A pseudogene of this gene is found on chromosome 5.[provided by RefSeq, Sep 2010]

PLEKHA1 links:

PLEKHA1 (HGNC:):

PLEKHA1 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.832

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLEKHA1	NM_001001974.4 linkuse as main transcript	c.698G>C	p.Arg233Pro	missense_variant	9/12	ENST00000368990.8	NP_001001974.1	Q9HB21-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PLEKHA1	ENST00000368990.8 linkuse as main transcript	c.698G>C	p.Arg233Pro	missense_variant	9/12	1	NM_001001974.4	ENSP00000357986.3		Q9HB21-1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

123744

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000451

AC:

AN:

221678

Hom.:

AF XY:

0.00000830

AC XY:

AN XY:

120518

show subpopulations

Gnomad AFR exome

AF:

0.0000653

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

123744

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

57458

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ExAC

AF:

0.00000824

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

1.0

BayesDel_addAF

Uncertain

0.12

BayesDel_noAF

Uncertain

0.12

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Pathogenic

0.90

D;D;D;.;D

Eigen

Pathogenic

0.76

Eigen_PC

Pathogenic

0.71

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Pathogenic

0.99

.;D;.;D;D

M_CAP

Benign

0.032

MetaRNN

Pathogenic

0.83

D;D;D;D;D

MetaSVM

Benign

-1.0

MutationAssessor

Pathogenic

3.2

M;.;M;M;M

PrimateAI

Pathogenic

0.81

PROVEAN

Pathogenic

-5.2

D;D;.;D;D

REVEL

Uncertain

0.55

Sift

Uncertain

0.0060

D;D;.;D;D

Sift4G

Uncertain

0.0040

D;D;D;D;D

Polyphen

1.0

D;.;D;.;D

Vest4

0.86

MutPred

0.64

Gain of methylation at K229 (P = 0.0457);Gain of methylation at K229 (P = 0.0457);Gain of methylation at K229 (P = 0.0457);Gain of methylation at K229 (P = 0.0457);Gain of methylation at K229 (P = 0.0457);

MVP

0.66

MPC

1.4

ClinPred

0.99

GERP RS

5.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.93

gMVP

0.88

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over