12-14535709-A-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_024829.6(PLBD1):ā€‹c.794T>Cā€‹(p.Val265Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000991 in 1,613,884 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 (ā˜…). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V265I) has been classified as Likely benign.

Frequency

Genomes: š‘“ 0.000026 ( 0 hom., cov: 33)
Exomes š‘“: 0.0000082 ( 0 hom. )

Consequence

PLBD1
NM_024829.6 missense

Scores

1
3
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.72
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 Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.016908258).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
PLBD1NM_024829.6 linkuse as main transcriptc.794T>C p.Val265Ala missense_variant 6/11 ENST00000240617.10 NP_079105.4
LOC101928317XR_001749015.2 linkuse as main transcriptn.397A>G non_coding_transcript_exon_variant 3/5

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
PLBD1ENST00000240617.10 linkuse as main transcriptc.794T>C p.Val265Ala missense_variant 6/111 NM_024829.6 ENSP00000240617 P1
ENST00000655882.1 linkuse as main transcriptn.412A>G non_coding_transcript_exon_variant 3/5
PLBD1ENST00000541800.6 linkuse as main transcriptn.417T>C non_coding_transcript_exon_variant 1/33
PLBD1ENST00000541618.1 linkuse as main transcriptc.*451T>C 3_prime_UTR_variant, NMD_transcript_variant 5/65 ENSP00000441278

Frequencies

GnomAD3 genomes
AF:
0.0000263
AC:
4
AN:
152124
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000772
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000636
AC:
16
AN:
251396
Hom.:
0
AF XY:
0.0000662
AC XY:
9
AN XY:
135872
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000870
Gnomad SAS 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:
0.00000821
AC:
12
AN:
1461642
Hom.:
0
Cov.:
29
AF XY:
0.0000124
AC XY:
9
AN XY:
727142
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000277
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000263
AC:
4
AN:
152242
Hom.:
0
Cov.:
33
AF XY:
0.0000269
AC XY:
2
AN XY:
74436
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000774
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000264
ExAC
AF:
0.0000741
AC:
9
Asia WGS
AF:
0.000289
AC:
1
AN:
3478

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 submitterclinical testingAmbry GeneticsNov 09, 2023The c.794T>C (p.V265A) alteration is located in exon 6 (coding exon 6) of the PLBD1 gene. This alteration results from a T to C substitution at nucleotide position 794, causing the valine (V) at amino acid position 265 to be replaced by an alanine (A). 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
Uncertain
0.40
BayesDel_addAF
Benign
-0.45
T
BayesDel_noAF
Benign
-0.51
CADD
Benign
23
DANN
Uncertain
0.99
DEOGEN2
Benign
0.0042
T
Eigen
Benign
-0.016
Eigen_PC
Benign
0.15
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Benign
0.57
T
M_CAP
Benign
0.013
T
MetaRNN
Benign
0.017
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.69
N
MutationTaster
Benign
1.0
N
PrimateAI
Uncertain
0.53
T
PROVEAN
Benign
-1.9
N
REVEL
Benign
0.17
Sift
Benign
0.14
T
Sift4G
Benign
0.23
T
Polyphen
0.082
B
Vest4
0.16
MVP
0.13
MPC
0.29
ClinPred
0.15
T
GERP RS
5.7
Varity_R
0.10
gMVP
0.71

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: rs200131855; hg19: chr12-14688643; API