chr12-14506992-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_024829.6(PLBD1):​c.1313G>A​(p.Arg438Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00499 in 1,613,944 control chromosomes in the GnomAD database, including 68 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0059 ( 8 hom., cov: 32)
Exomes 𝑓: 0.0049 ( 60 hom. )

Consequence

PLBD1
NM_024829.6 missense

Scores

6
5
8

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 7.38
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.01349023).
BP6
Variant 12-14506992-C-T is Benign according to our data. Variant chr12-14506992-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2642755.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
High Homozygotes in GnomAd4 at 8 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
PLBD1NM_024829.6 linkuse as main transcriptc.1313G>A p.Arg438Gln missense_variant 9/11 ENST00000240617.10 NP_079105.4

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
PLBD1ENST00000240617.10 linkuse as main transcriptc.1313G>A p.Arg438Gln missense_variant 9/111 NM_024829.6 ENSP00000240617 P1

Frequencies

GnomAD3 genomes
AF:
0.00588
AC:
894
AN:
152002
Hom.:
8
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000942
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00459
Gnomad ASJ
AF:
0.0415
Gnomad EAS
AF:
0.000387
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00737
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00809
Gnomad OTH
AF:
0.00528
GnomAD3 exomes
AF:
0.00612
AC:
1539
AN:
251348
Hom.:
21
AF XY:
0.00593
AC XY:
806
AN XY:
135836
show subpopulations
Gnomad AFR exome
AF:
0.00105
Gnomad AMR exome
AF:
0.00237
Gnomad ASJ exome
AF:
0.0428
Gnomad EAS exome
AF:
0.0000544
Gnomad SAS exome
AF:
0.0000327
Gnomad FIN exome
AF:
0.00674
Gnomad NFE exome
AF:
0.00726
Gnomad OTH exome
AF:
0.00587
GnomAD4 exome
AF:
0.00489
AC:
7152
AN:
1461826
Hom.:
60
Cov.:
30
AF XY:
0.00490
AC XY:
3567
AN XY:
727222
show subpopulations
Gnomad4 AFR exome
AF:
0.000657
Gnomad4 AMR exome
AF:
0.00248
Gnomad4 ASJ exome
AF:
0.0407
Gnomad4 EAS exome
AF:
0.0000504
Gnomad4 SAS exome
AF:
0.0000696
Gnomad4 FIN exome
AF:
0.00640
Gnomad4 NFE exome
AF:
0.00471
Gnomad4 OTH exome
AF:
0.00604
GnomAD4 genome
AF:
0.00588
AC:
894
AN:
152118
Hom.:
8
Cov.:
32
AF XY:
0.00573
AC XY:
426
AN XY:
74348
show subpopulations
Gnomad4 AFR
AF:
0.000939
Gnomad4 AMR
AF:
0.00458
Gnomad4 ASJ
AF:
0.0415
Gnomad4 EAS
AF:
0.000387
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00737
Gnomad4 NFE
AF:
0.00809
Gnomad4 OTH
AF:
0.00523
Alfa
AF:
0.00819
Hom.:
23
Bravo
AF:
0.00502
TwinsUK
AF:
0.00243
AC:
9
ALSPAC
AF:
0.00182
AC:
7
ESP6500AA
AF:
0.00159
AC:
7
ESP6500EA
AF:
0.00919
AC:
79
ExAC
AF:
0.00590
AC:
716
Asia WGS
AF:
0.00173
AC:
6
AN:
3478
EpiCase
AF:
0.00736
EpiControl
AF:
0.00587

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Likely benign, criteria provided, single submitterclinical testingCeGaT Center for Human Genetics TuebingenJan 01, 2023PLBD1: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.26
BayesDel_addAF
Benign
-0.23
T
BayesDel_noAF
Benign
-0.10
CADD
Pathogenic
31
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.021
T
Eigen
Pathogenic
0.84
Eigen_PC
Pathogenic
0.80
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Pathogenic
0.98
D
M_CAP
Uncertain
0.090
D
MetaRNN
Benign
0.013
T
MetaSVM
Benign
-0.91
T
MutationAssessor
Uncertain
2.8
M
MutationTaster
Benign
1.0
D
PrimateAI
Benign
0.46
T
PROVEAN
Uncertain
-3.7
D
REVEL
Uncertain
0.53
Sift
Uncertain
0.0040
D
Sift4G
Pathogenic
0.0
D
Polyphen
1.0
D
Vest4
0.75
MVP
0.55
MPC
0.84
ClinPred
0.040
T
GERP RS
5.4
Varity_R
0.63
gMVP
0.74

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.

Other links and lift over

dbSNP: rs75778757; hg19: chr12-14659926; COSMIC: COSV53696084; COSMIC: COSV53696084; API