chr3-155481027-A-C

Position:

• chr3-155481027-A-C

Variant summary

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

The NM_014996.4(PLCH1):​c.4999T>G​(p.Leu1667Val) 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: 33)
• Consequence: PLCH1 NM_014996.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.439

Genes affected

PLCH1 (HGNC:29185): (phospholipase C eta 1) PLCH1 is a member of the PLC-eta family of the phosphoinositide-specific phospholipase C (PLC) superfamily of enzymes that cleave phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2) to generate second messengers inositol 1,4,5-trisphosphate (IP3) and diacylglycerol (DAG) (Hwang et al., 2005 [PubMed 15702972]).[supplied by OMIM, Jun 2009]

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=0.09545985).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLCH1	NM_014996.4	c.4999T>G	p.Leu1667Val	missense_variant	23/23	ENST00000460012.7	NP_055811.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PLCH1	ENST00000460012.7	c.4999T>G	p.Leu1667Val	missense_variant	23/23	5	NM_014996.4	ENSP00000417502.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

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

Jun 17, 2024

The c.5023T>G (p.L1675V) alteration is located in exon 23 (coding exon 23) of the PLCH1 gene. This alteration results from a T to G substitution at nucleotide position 5023, causing the leucine (L) at amino acid position 1675 to be replaced by a valine (V). 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	0.086
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	13
DANN	Benign	0.96
DEOGEN2	Benign	0.053	.;T;.
Eigen	Benign	-0.89
Eigen_PC	Benign	-0.92
FATHMM_MKL	Benign	0.24	N
LIST_S2	Benign	0.73	T;T;T
M_CAP	Benign	0.0067	T
MetaRNN	Benign	0.095	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.8	.;L;.
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-1.0	.;N;N
REVEL	Benign	0.077
Sift	Benign	0.057	.;T;T
Sift4G	Benign	0.18	.;T;T
Polyphen		0.022, 0.037	.;B;B
Vest4		0.16, 0.11
MutPred		0.21		.;Loss of glycosylation at P1679 (P = 0.034);.;
MVP		0.54
MPC		0.047
ClinPred		0.13	T
GERP RS		-4.3
Varity_R		0.049
gMVP		0.19

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: chr3-155198816;