12-14536608-T-C

Position:

• chr12-14536608-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_024829.6(PLBD1):​c.661A>G​(p.Lys221Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 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)
• Consequence: PLBD1 NM_024829.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.57

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]

(HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07990584).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLBD1	NM_024829.6	c.661A>G	p.Lys221Glu	missense_variant	5/11	ENST00000240617.10	NP_079105.4
LOC101928317	XR_001749015.2	n.588+708T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PLBD1	ENST00000240617.10	c.661A>G	p.Lys221Glu	missense_variant	5/11	1	NM_024829.6	ENSP00000240617	P1
	ENST00000655882.1	n.603+708T>C		intron_variant, non_coding_transcript_variant
PLBD1	ENST00000541618.1	c.*318A>G		3_prime_UTR_variant, NMD_transcript_variant	4/6	5		ENSP00000441278

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 15, 2023

The c.661A>G (p.K221E) alteration is located in exon 5 (coding exon 5) of the PLBD1 gene. This alteration results from a A to G substitution at nucleotide position 661, causing the lysine (K) at amino acid position 221 to be replaced by a glutamic acid (E). 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	Benign	0.11
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	16
DANN	Benign	0.58
DEOGEN2	Benign	0.0014	T
Eigen	Benign	-0.93
Eigen_PC	Benign	-0.82
FATHMM_MKL	Benign	0.062	N
LIST_S2	Benign	0.58	T
M_CAP	Benign	0.0071	T
MetaRNN	Benign	0.080	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	1.2	L
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-0.30	N
REVEL	Benign	0.058
Sift	Benign	0.56	T
Sift4G	Benign	0.65	T
Polyphen		0.0090	B
Vest4		0.26
MutPred		0.50		Loss of methylation at K221 (P = 4e-04);
MVP		0.055
MPC		0.29
ClinPred		0.098	T
GERP RS		3.5
Varity_R		0.095
gMVP		0.63

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: chr12-14689542;