Variant 11-73650669-A-G 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.211A>G(p.Asn71Asp) variant causes a missense change. The variant allele was found at a frequency of 0.0000535 in 1,458,094 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)

Exomes 𝑓: 0.000053 ( 0 hom. )

Consequence

PLEKHB1
NM_021200.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.99

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:

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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=0.24813887).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLEKHB1	NM_021200.3 linkuse as main transcript	c.211A>G	p.Asn71Asp	missense_variant	3/8	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.211A>G	p.Asn71Asp	missense_variant	3/8	1	NM_021200.3	ENSP00000346127.5		Q9UF11-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000414

AC:

AN:

241652

Hom.:

AF XY:

0.00000763

AC XY:

AN XY:

131020

show subpopulations

Gnomad AFR exome

AF:

0.00

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:

0.00000915

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000535

AC:

AN:

1458094

Hom.:

Cov.:

AF XY:

0.0000497

AC XY:

AN XY:

724906

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:

0.0000685

Gnomad4 OTH exome

AF:

0.0000332

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000113

ExAC

AF:

0.00000825

AC:

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

Aug 14, 2024

The c.211A>G (p.N71D) alteration is located in exon 3 (coding exon 3) of the PLEKHB1 gene. This alteration results from a A to G substitution at nucleotide position 211, causing the asparagine (N) at amino acid position 71 to be replaced by an aspartic acid (D). 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

Uncertain

0.37

BayesDel_addAF

Uncertain

0.14

BayesDel_noAF

Uncertain

-0.040

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.17

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

Eigen

Benign

0.11

Eigen_PC

Uncertain

0.26

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.86

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

M_CAP

Uncertain

0.13

MetaRNN

Benign

0.25

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

MetaSVM

Uncertain

0.29

MutationAssessor

Benign

0.58

N;N;.;.;.;.;.;.;.;.;.;.;.;.;.

PrimateAI

Uncertain

0.67

PROVEAN

Benign

1.0

N;N;N;N;N;N;N;N;N;N;N;N;N;N;N

REVEL

Benign

0.18

Sift

Benign

1.0

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

Sift4G

Benign

0.89

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

Polyphen

0.89

P;P;.;.;.;.;.;.;.;.;.;.;.;.;.

Vest4

0.52

MutPred

0.28

Gain of sheet (P = 0.0028);Gain of sheet (P = 0.0028);.;.;.;.;.;.;.;.;.;.;.;.;.;

MVP

0.93

MPC

0.78

ClinPred

0.84

GERP RS

5.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.093

gMVP

0.23

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