Variant 11-73660843-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_021200.3(PLEKHB1):c.586C>T(p.Pro196Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000315 in 1,586,658 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

PLEKHB1
NM_021200.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.18

Variant links:

Genes affected

PLEKHB1 (HGNC:19079): (pleckstrin homology domain containing B1) Predicted to enable protein C-terminus binding activity and protein homodimerization activity. Predicted to be involved in regulation of cell differentiation. Is integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

PLEKHB1 links:

PLEKHB1 (HGNC:):

PLEKHB1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.17364177).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLEKHB1	NM_021200.3 linkuse as main transcript	c.586C>T	p.Pro196Ser	missense_variant	7/8	ENST00000354190.10	NP_067023.1	Q9UF11-1A0A024R5H9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PLEKHB1	ENST00000354190.10 linkuse as main transcript	c.586C>T	p.Pro196Ser	missense_variant	7/8	1	NM_021200.3	ENSP00000346127.5		Q9UF11-1

Frequencies

GnomAD3 genomes

AF:

0.0000133

AC:

AN:

150780

Hom.:

Cov.:

show subpopulations

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:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000209

AC:

AN:

1435878

Hom.:

Cov.:

AF XY:

0.00000140

AC XY:

AN XY:

711986

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000272

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000133

AC:

AN:

150780

Hom.:

Cov.:

AF XY:

0.0000136

AC XY:

AN XY:

73706

show subpopulations

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:

0.0000294

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000612

Hom.:

Bravo

AF:

0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 19, 2024

The c.586C>T (p.P196S) alteration is located in exon 7 (coding exon 7) of the PLEKHB1 gene. This alteration results from a C to T substitution at nucleotide position 586, causing the proline (P) at amino acid position 196 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.062

BayesDel_addAF

Benign

-0.0029

BayesDel_noAF

Benign

-0.24

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.25

T;.;.;.;.;T;T;T;.;T

Eigen

Benign

-0.25

Eigen_PC

Benign

-0.25

FATHMM_MKL

Benign

0.27

LIST_S2

Uncertain

0.90

D;D;.;D;D;D;D;D;D;D

M_CAP

Benign

0.0064

MetaRNN

Benign

0.17

T;T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-1.0

PrimateAI

Uncertain

0.55

PROVEAN

Benign

-1.6

N;N;N;N;D;N;N;N;N;N

REVEL

Benign

0.048

Sift

Benign

0.066

T;D;D;T;D;D;D;D;D;D

Sift4G

Benign

0.12

T;T;T;T;T;T;T;T;T;T

Polyphen

0.89

P;B;.;.;.;.;.;.;.;.

Vest4

0.31

MutPred

0.33

Gain of sheet (P = 0.0266);.;.;.;.;.;.;.;.;.;

MVP

0.25

MPC

0.18

ClinPred

0.84

GERP RS

3.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.096

gMVP

0.77

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over