chr12-14511556-C-G

Variant names:

• chr12-14511556-C-G
• rs1278166864
• NM_024829.6:c.1000G>C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_024829.6(PLBD1):​c.1000G>C​(p.Asp334His) 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: -0.868

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.047716886).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLBD1	NM_024829.6	c.1000G>C	p.Asp334His	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.1000G>C	p.Asp334His	missense_variant	Exon 7 of 11	1	NM_024829.6	ENSP00000240617.5
PLBD1	ENST00000541618.1	n.*657G>C		non_coding_transcript_exon_variant	Exon 6 of 6	5		ENSP00000441278.1
PLBD1	ENST00000541800.6	n.623G>C		non_coding_transcript_exon_variant	Exon 2 of 3	3
PLBD1	ENST00000541618.1	n.*657G>C		3_prime_UTR_variant	Exon 6 of 6	5		ENSP00000441278.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000282 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 10, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1000G>C (p.D334H) alteration is located in exon 7 (coding exon 7) of the PLBD1 gene. This alteration results from a G to C substitution at nucleotide position 1000, causing the aspartic acid (D) at amino acid position 334 to be replaced by a histidine (H). 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	0.13
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	0.84
DANN	Benign	0.87
DEOGEN2	Benign	0.00064	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.044	N
LIST_S2	Benign	0.75	T
M_CAP	Benign	0.0074	T
MetaRNN	Benign	0.048	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.4	L
PrimateAI	Benign	0.22	T
PROVEAN	Benign	-0.65	N
REVEL	Benign	0.011
Sift	Benign	0.24	T
Sift4G	Benign	0.18	T
Polyphen		0.0010	B
Vest4		0.12
MutPred		0.28		Loss of ubiquitination at K337 (P = 0.0344);
MVP		0.061
MPC		0.25
ClinPred		0.038	T
GERP RS		-5.7
Varity_R		0.047
gMVP		0.52

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

LitVar

Other links and lift over

dbSNP: rs1278166864; hg19: chr12-14664490;