Genetic Variant NM_024829.6:c.74T>C (chr12-14567623-A-G) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -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. 15/22 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

Publications

2 publications found

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 was made for transcript

Our verdict: Likely_benign. The variant received -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 VariationId is 3214347.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024829.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLBD1	NM_024829.6	MANE Select	c.74T>C	p.Leu25Pro	missense	Exon 1 of 11	NP_079105.4
	PLBD1-AS1	NR_120465.1		n.-109A>G		upstream_gene	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PLBD1	ENST00000240617.10	TSL:1 MANE Select	c.74T>C	p.Leu25Pro	missense	Exon 1 of 11	ENSP00000240617.5	Q6P4A8
PLBD1	ENST00000918098.1		c.74T>C	p.Leu25Pro	missense	Exon 1 of 12	ENSP00000588157.1
PLBD1	ENST00000945093.1		c.74T>C	p.Leu25Pro	missense	Exon 1 of 11	ENSP00000615152.1

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

GnomAD2 exomes

AF:

0.0000353

AC:

AN:

56624

AF XY:

0.0000605

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 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

African (AFR)

AF:

0.00414

AC:

AN:

4106

American (AMR)

AF:

0.00

AC:

AN:

3328

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

1798

East Asian (EAS)

AF:

0.00

AC:

AN:

2020

South Asian (SAS)

AF:

0.00187

AC:

AN:

2138

European-Finnish (FIN)

AF:

0.00

AC:

AN:

3652

Middle Eastern (MID)

AF:

0.00

AC:

AN:

352

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

140304

Other (OTH)

AF:

0.00

AC:

AN:

6136

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00160

AC:

AN:

18692

Hom.:

Cov.:

AF XY:

0.00142

AC XY:

AN XY:

9156

show subpopulations

African (AFR)

AF:

0.00400

AC:

AN:

6996

American (AMR)

AF:

0.000459

AC:

AN:

2180

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

234

East Asian (EAS)

AF:

0.00

AC:

AN:

274

South Asian (SAS)

AF:

0.00

AC:

AN:

European-Finnish (FIN)

AF:

0.00

AC:

AN:

1448

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

7140

Other (OTH)

AF:

0.00481

AC:

AN:

208

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.55

CADD

Benign

9.1

(source)

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

PhyloP100

-0.58

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

PromoterAI

-0.011

Neutral

(source)

Varity_R

0.084

gMVP

0.65

Mutation Taster

=93/7

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over