Variant chr12-14567623-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The NM_024829.6(PLBD1):c.74T>C(p.Leu25Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0016 ( 0 hom., cov: 0)

Exomes 𝑓: 0.00013 ( 0 hom. )

Consequence

PLBD1
NM_024829.6 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.579

Variant links:

Genes affected

PLBD1 (HGNC:26215): (phospholipase B domain containing 1) Predicted to enable phospholipase activity. Predicted to be involved in phospholipid catabolic process. Located in extracellular space. [provided by Alliance of Genome Resources, Apr 2022]

PLBD1 links:

PLBD1-AS1 (HGNC:51143): (PLBD1 antisense RNA 1)

PLBD1-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.017659664).

BP6

Variant 12-14567623-A-G is Benign according to our data. Variant chr12-14567623-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 3214347.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLBD1	NM_024829.6 linkuse as main transcript	c.74T>C	p.Leu25Pro	missense_variant	1/11	ENST00000240617.10	NP_079105.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
PLBD1	ENST00000240617.10 linkuse as main transcript	c.74T>C	p.Leu25Pro	missense_variant	1/11	1	NM_024829.6	ENSP00000240617	P1
PLBD1-AS1	ENST00000660979.1 linkuse as main transcript	n.162A>G		non_coding_transcript_exon_variant	1/4
PLBD1-AS1	ENST00000542401.2 linkuse as main transcript	n.231A>G		non_coding_transcript_exon_variant	1/5	4
PLBD1	ENST00000541618.1 linkuse as main transcript	c.74T>C	p.Leu25Pro	missense_variant, NMD_transcript_variant	1/6	5		ENSP00000441278

Frequencies

GnomAD3 genomes

AF:

0.00161

AC:

AN:

18640

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00403

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000460

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:

0.00481

GnomAD3 exomes

AF:

0.0000353

AC:

AN:

56624

Hom.:

AF XY:

0.0000605

AC XY:

AN XY:

33078

show subpopulations

Gnomad AFR exome

AF:

0.000943

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000675

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000128

AC:

AN:

163834

Hom.:

Cov.:

AF XY:

0.000142

AC XY:

AN XY:

77628

show subpopulations

Gnomad4 AFR exome

AF:

0.00414

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00187

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00160

AC:

AN:

18692

Hom.:

Cov.:

AF XY:

0.00142

AC XY:

AN XY:

9156

show subpopulations

Gnomad4 AFR

AF:

0.00400

Gnomad4 AMR

AF:

0.000459

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:

0.00481

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 09, 2024

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.55

CADD

Benign

9.1

DANN

Benign

0.51

DEOGEN2

Benign

0.0048

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.038

LIST_S2

Benign

0.14

M_CAP

Benign

0.0070

MetaRNN

Benign

0.018

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.69

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.61

PROVEAN

Benign

-0.54

REVEL

Benign

0.059

Sift

Benign

0.049

Sift4G

Benign

0.075

Polyphen

0.0

Vest4

0.21

MVP

0.067

MPC

0.32

ClinPred

0.013

GERP RS

-2.5

Varity_R

0.084

gMVP

0.65

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