chr12-14511335-T-C

Variant names:

• chr12-14511335-T-C
• rs1945296704
• NM_024829.6:c.1111A>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_024829.6(PLBD1):​c.1111A>G​(p.Lys371Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,460,856 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: PLBD1 NM_024829.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.758
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.030213475).

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.1111A>G	p.Lys371Glu	missense	Exon 8 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.1111A>G	p.Lys371Glu	missense	Exon 8 of 11	ENSP00000240617.5	Q6P4A8
	PLBD1	ENST00000918098.1		c.1270A>G	p.Lys424Glu	missense	Exon 9 of 12	ENSP00000588157.1
	PLBD1	ENST00000945093.1		c.1108A>G	p.Lys370Glu	missense	Exon 8 of 11	ENSP00000615152.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1460856 Hom.: 0 Cov.: 34 AF XY: 0.00000275 AC XY: 2 AN XY: 726834

African (AFR) AF: 0.00 AC: 0 AN: 33434

American (AMR) AF: 0.00 AC: 0 AN: 44654

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26114

East Asian (EAS) AF: 0.00 AC: 0 AN: 39686

South Asian (SAS) AF: 0.00 AC: 0 AN: 86164

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53406

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00000270 AC: 3 AN: 1111274

Other (OTH) AF: 0.00 AC: 0 AN: 60358

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000468 Hom.: 0

ClinVar

ClinVar submissions

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	Benign	0.063
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.76
CADD	Benign	9.4
DANN	Benign	0.93
DEOGEN2	Benign	0.0016	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.048	N
LIST_S2	Benign	0.60	T
M_CAP	Benign	0.0076	T
MetaRNN	Benign	0.030	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.1	L
PhyloP100		0.76
PrimateAI	Benign	0.23	T
PROVEAN	Benign	0.99	N
REVEL	Benign	0.026
Sift	Benign	0.30	T
Sift4G	Benign	0.21	T
Polyphen		0.0050	B
Vest4		0.072
MutPred		0.43		Gain of catalytic residue at D370 (P = 0.0025)
MVP		0.10
MPC		0.28
ClinPred		0.13	T
GERP RS		-0.64
Varity_R		0.051
gMVP		0.54
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: rs1945296704; hg19: chr12-14664269;