Variant 12-113358658-G-A 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_173542.4(PLBD2):c.58G>A(p.Ala20Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

PLBD2
NM_173542.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.82

Variant links:

Genes affected

PLBD2 (HGNC:27283): (phospholipase B domain containing 2) Predicted to enable phospholipase activity. Predicted to be involved in phospholipid catabolic process. Located in extracellular exosome. [provided by Alliance of Genome Resources, Apr 2022]

PLBD2 links:

SLC8B1 (HGNC:26175): (solute carrier family 8 member B1) SLC24A6 belongs to a family of potassium-dependent sodium/calcium exchangers that maintain cellular calcium homeostasis through the electrogenic countertransport of 4 sodium ions for 1 calcium ion and 1 potassium ion (Cai and Lytton, 2004 [PubMed 14625281]).[supplied by OMIM, Mar 2008]

SLC8B1 links:

LOC105369989 (HGNC:):

LOC105369989 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=0.15619418).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLBD2	NM_173542.4 link	c.58G>A	p.Ala20Thr	missense_variant	1/12	ENST00000280800.5	NP_775813.2	Q8NHP8-1
PLBD2	NM_001159727.2 link	c.58G>A	p.Ala20Thr	missense_variant	1/11		NP_001153199.1	Q8NHP8-2
PLBD2	XM_017018977.2 link	c.-242G>A		5_prime_UTR_variant	1/11		XP_016874466.1
LOC105369989	XR_945346.3 link	n.181+672C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
PLBD2	ENST00000280800.5 link	c.58G>A	p.Ala20Thr	missense_variant	1/12	1	NM_173542.4	ENSP00000280800.3	Q8NHP8-1
PLBD2	ENST00000545182.6 link	c.58G>A	p.Ala20Thr	missense_variant	1/11	2		ENSP00000443463.2	Q8NHP8-2
SLC8B1	ENST00000549372.1 link	c.-83+672C>T		intron_variant		5		ENSP00000447972.1	F8VTU4
SLC8B1	ENST00000548518.1 link	n.137+672C>T		intron_variant		4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1308876

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

644684

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:

0.00

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

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 29, 2024

The c.58G>A (p.A20T) alteration is located in exon 1 (coding exon 1) of the PLBD2 gene. This alteration results from a G to A substitution at nucleotide position 58, causing the alanine (A) at amino acid position 20 to be replaced by a threonine (T). 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

0.13

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.56

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0098

.;T

Eigen

Benign

-0.56

Eigen_PC

Benign

-0.46

FATHMM_MKL

Benign

0.43

LIST_S2

Benign

0.69

T;T

M_CAP

Pathogenic

0.40

MetaRNN

Benign

0.16

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.90

L;L

PrimateAI

Pathogenic

0.79

PROVEAN

Benign

-0.26

N;N

REVEL

Benign

0.020

Sift

Benign

0.29

T;T

Sift4G

Benign

0.25

T;T

Polyphen

0.0030

.;B

Vest4

0.23

MutPred

0.38

Gain of catalytic residue at A20 (P = 0.0806);Gain of catalytic residue at A20 (P = 0.0806);

MVP

0.23

MPC

1.1

ClinPred

0.52

GERP RS

3.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Varity_R

0.060

gMVP

0.39

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