chr12-14511699-G-A

Variant names:

• chr12-14511699-G-A
• NM_024829.6:c.857C>T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_024829.6(PLBD1):​c.857C>T​(p.Ser286Phe) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,778 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: PLBD1 NM_024829.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.27

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.936

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLBD1	NM_024829.6	c.857C>T	p.Ser286Phe	missense_variant	Exon 7 of 11	ENST00000240617.10	NP_079105.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLBD1	ENST00000240617.10	c.857C>T	p.Ser286Phe	missense_variant	Exon 7 of 11	1	NM_024829.6	ENSP00000240617.5
PLBD1	ENST00000541618.1	n.*514C>T		non_coding_transcript_exon_variant	Exon 6 of 6	5		ENSP00000441278.1
PLBD1	ENST00000541800.6	n.480C>T		non_coding_transcript_exon_variant	Exon 2 of 3	3
PLBD1	ENST00000541618.1	n.*514C>T		3_prime_UTR_variant	Exon 6 of 6	5		ENSP00000441278.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1461778 Hom.: 0 Cov.: 34 AF XY: 0.00000275 AC XY: 2 AN XY: 727202

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000894

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.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	1.0
BayesDel_addAF	Pathogenic	0.32	D
BayesDel_noAF	Pathogenic	0.22
CADD	Pathogenic	29
DANN	Uncertain	1.0
DEOGEN2	Benign	0.22	T
Eigen	Pathogenic	1.0
Eigen_PC	Pathogenic	0.95
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Pathogenic	0.98	D
M_CAP	Benign	0.074	D
MetaRNN	Pathogenic	0.94	D
MetaSVM	Uncertain	-0.013	T
MutationAssessor	Pathogenic	4.2	H
PrimateAI	Uncertain	0.74	T
PROVEAN	Pathogenic	-5.7	D
REVEL	Pathogenic	0.78
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.97
MutPred		0.82		Loss of disorder (P = 0.0333);
MVP		0.45
MPC		0.81
ClinPred		1.0	D
GERP RS		5.5
Varity_R		0.89
gMVP		0.97

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.

Other links and lift over

hg19: chr12-14664633; COSMIC: COSV53692619;