rs762382039

Variant names:

• chr12-14507100-T-C
• rs762382039
• NM_024829.6:c.1205A>G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 1P and 0B. PP3

The NM_024829.6(PLBD1):​c.1205A>G​(p.Asn402Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000205 in 1,609,314 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000066 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000016 (0 hom.)
• Consequence: PLBD1 NM_024829.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.74
• Publications: 2 publications found

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

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PP3: MetaRNN computational evidence supports a deleterious effect, 0.83

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.1205A>G	p.Asn402Ser	missense	Exon 9 of 11	NP_079105.4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLBD1	ENST00000240617.10	TSL:1 MANE Select	c.1205A>G	p.Asn402Ser	missense	Exon 9 of 11	ENSP00000240617.5	Q6P4A8
	PLBD1	ENST00000918098.1		c.1364A>G	p.Asn455Ser	missense	Exon 10 of 12	ENSP00000588157.1
	PLBD1	ENST00000945093.1		c.1202A>G	p.Asn401Ser	missense	Exon 9 of 11	ENSP00000615152.1

Frequencies

GnomAD3 genomes AF: 0.0000658 AC: 10 AN: 151920 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000656

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: 0.00

GnomAD2 exomes AF: 0.0000200 AC: 5 AN: 249888 AF XY: 0.0000370

Gnomad AFR exome AF: 0.0000616

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000109

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000883

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000158 AC: 23 AN: 1457394 Hom.: 0 Cov.: 30 AF XY: 0.0000138 AC XY: 10 AN XY: 725056

African (AFR) AF: 0.0000300 AC: 1 AN: 33380

American (AMR) AF: 0.0000674 AC: 3 AN: 44530

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26048

East Asian (EAS) AF: 0.00 AC: 0 AN: 39604

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 85854

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53358

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5760

European-Non Finnish (NFE) AF: 0.0000126 AC: 14 AN: 1108644

Other (OTH) AF: 0.0000664 AC: 4 AN: 60216

GnomAD4 genome AF: 0.0000658 AC: 10 AN: 151920 Hom.: 0 Cov.: 33 AF XY: 0.0000809 AC XY: 6 AN XY: 74180

African (AFR) AF: 0.00 AC: 0 AN: 41342

American (AMR) AF: 0.000656 AC: 10 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00 AC: 0 AN: 4806

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10566

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67994

Other (OTH) AF: 0.00 AC: 0 AN: 2088

Alfa AF: 0.0000447 Hom.: 0

Bravo AF: 0.000151

ExAC AF: 0.0000247 AC: 3

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.55
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.26
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.14	T
Eigen	Pathogenic	0.92
Eigen_PC	Pathogenic	0.83
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.95	D
M_CAP	Uncertain	0.099	D
MetaRNN	Pathogenic	0.83	D
MetaSVM	Uncertain	-0.24	T
MutationAssessor	Pathogenic	4.2	H
PhyloP100		5.7
PrimateAI	Benign	0.47	T
PROVEAN	Pathogenic	-5.0	D
REVEL	Uncertain	0.53
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.80
MVP		0.33
MPC		0.68
ClinPred		1.0	D
GERP RS		5.5
Varity_R		0.80
gMVP		0.83
Mutation Taster		=44/56	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.14		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs762382039; hg19: chr12-14660034;