Variant chr20-9362969-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 3P and 1B. PM2PP2BP4

The NM_001377142.1(PLCB4):c.443A>G(p.Lys148Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000689 in 1,451,650 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

PLCB4
NM_001377142.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.68

Variant links:

Genes affected

PLCB4 (HGNC:9059): (phospholipase C beta 4) The protein encoded by this gene catalyzes the formation of inositol 1,4,5-trisphosphate and diacylglycerol from phosphatidylinositol 4,5-bisphosphate. This reaction uses calcium as a cofactor and plays an important role in the intracellular transduction of many extracellular signals in the retina. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Feb 2010]

PLCB4 links:

PLCB4 (HGNC:):

PLCB4 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP2

Missense variant in gene, where missense usually causes diseases (based on misZ statistic), PLCB4. . Gene score misZ 3.5718 (greater than the threshold 3.09). Trascript score misZ 3.2758 (greater than threshold 3.09). GenCC has associacion of gene with auriculocondylar syndrome 1, auriculocondylar syndrome, auriculocondylar syndrome 2.

BP4

Computational evidence support a benign effect (MetaRNN=0.372873).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLCB4	NM_001377142.1 linkuse as main transcript	c.443A>G	p.Lys148Arg	missense_variant	8/40	ENST00000378473.9	NP_001364071.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PLCB4	ENST00000378473.9 linkuse as main transcript	c.443A>G	p.Lys148Arg	missense_variant	8/40	1	NM_001377142.1	ENSP00000367734.5		A0A7P0MRI8

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.89e-7

AC:

AN:

1451650

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

722874

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:

9.07e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 27, 2023

The c.443A>G (p.K148R) alteration is located in exon 5 (coding exon 5) of the PLCB4 gene. This alteration results from a A to G substitution at nucleotide position 443, causing the lysine (K) at amino acid position 148 to be replaced by an arginine (R). 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

0.079

BayesDel_addAF

Benign

-0.055

BayesDel_noAF

Benign

-0.32

CADD

Uncertain

DANN

Uncertain

0.98

DEOGEN2

Benign

0.22

.;T;.;T;.

Eigen

Benign

0.13

Eigen_PC

Uncertain

0.32

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.96

D;D;.;.;D

M_CAP

Benign

0.015

MetaRNN

Benign

0.37

T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.3

L;L;L;L;L

PrimateAI

Pathogenic

0.81

PROVEAN

Benign

-0.79

N;N;.;N;N

REVEL

Benign

0.13

Sift

Benign

0.56

T;T;.;T;T

Sift4G

Benign

0.68

T;T;T;T;T

Polyphen

0.61, 0.0070

.;P;.;P;B

Vest4

0.60

MutPred

0.39

Gain of MoRF binding (P = 0.0779);Gain of MoRF binding (P = 0.0779);Gain of MoRF binding (P = 0.0779);Gain of MoRF binding (P = 0.0779);Gain of MoRF binding (P = 0.0779);

MVP

0.66

MPC

0.58

ClinPred

0.61

GERP RS

5.9

Varity_R

0.16

gMVP

0.34

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over