12-14567623-A-C

Variant names:

• chr12-14567623-A-C
• rs773839439
• NM_024829.6:c.74T>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_024829.6(PLBD1):​c.74T>G​(p.Leu25Arg) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L25P) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 0)
• Consequence: PLBD1 NM_024829.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.579
• 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]

PLBD1-AS1 (HGNC:51143): (PLBD1 antisense RNA 1)

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.19258216).

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>G	p.Leu25Arg	missense	Exon 1 of 11	NP_079105.4
	PLBD1-AS1	NR_120465.1		n.-109A>C		upstream_gene	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLBD1	ENST00000240617.10	TSL:1 MANE Select	c.74T>G	p.Leu25Arg	missense	Exon 1 of 11	ENSP00000240617.5	Q6P4A8
	PLBD1	ENST00000918098.1		c.74T>G	p.Leu25Arg	missense	Exon 1 of 12	ENSP00000588157.1
	PLBD1	ENST00000945093.1		c.74T>G	p.Leu25Arg	missense	Exon 1 of 11	ENSP00000615152.1

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD4 exome Cov.: 0

GnomAD4 genome Cov.: 0

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	9.6
DANN	Benign	0.75
DEOGEN2	Benign	0.0031	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.099	N
LIST_S2	Benign	0.18	T
M_CAP	Benign	0.0067	T
MetaRNN	Benign	0.19	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.69	N
PhyloP100		-0.58
PrimateAI	Uncertain	0.61	T
PROVEAN	Benign	-0.27	N
REVEL	Benign	0.23
Sift	Benign	0.060	T
Sift4G	Benign	0.10	T
Polyphen		0.16	B
Vest4		0.23
MutPred		0.63		Gain of sheet (P = 0.0344)
MVP		0.081
MPC		0.29
ClinPred		0.11	T
GERP RS		-2.5
PromoterAI		0.0048	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.090
gMVP		0.67
Mutation Taster		=93/7	polymorphism

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

Other links and lift over

dbSNP: rs773839439; hg19: chr12-14720557;