NM_014638.4:c.118C>G

Variant names:

• chr1-2476706-C-G
• NM_014638.4:c.118C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_014638.4(PLCH2):​c.118C>G​(p.Pro40Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000688 in 1,454,284 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: PLCH2 NM_014638.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.48
• Publications: 0 publications found

Genes affected

PLCH2 (HGNC:29037): (phospholipase C eta 2) PLCH2 is a member of the PLC-eta family of the phosphoinositide-specific phospholipase C (PLC) superfamily of enzymes that cleave PtdIns(4,5) P2 to generate second messengers inositol 1,4,5-trisphosphate and diacylglycerol (Zhou et al., 2005 [PubMed 16107206]).[supplied by OMIM, Jun 2009]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08030614).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014638.4. 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
	PLCH2	NM_014638.4	MANE Select	c.118C>G	p.Pro40Ala	missense	Exon 1 of 22	NP_055453.2
	PLCH2	NM_001303013.1		c.-815C>G		5_prime_UTR	Exon 1 of 22	NP_001289942.1	O75038
	PLCH2	NM_001303012.2		c.44-1770C>G		intron	N/A	NP_001289941.1	O75038-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLCH2	ENST00000378486.8	TSL:1 MANE Select	c.118C>G	p.Pro40Ala	missense	Exon 1 of 22	ENSP00000367747.3	O75038-1
	PLCH2	ENST00000419816.6	TSL:5	c.118C>G	p.Pro40Ala	missense	Exon 1 of 22	ENSP00000389803.2	O75038-1
	PLCH2	ENST00000449969.5	TSL:5	c.44-1770C>G		intron	N/A	ENSP00000397289.1	O75038-2

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 6.88e-7 AC: 1 AN: 1454284 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 723472

African (AFR) AF: 0.00 AC: 0 AN: 33274

American (AMR) AF: 0.00 AC: 0 AN: 43980

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25812

East Asian (EAS) AF: 0.00 AC: 0 AN: 39486

South Asian (SAS) AF: 0.00 AC: 0 AN: 85566

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51298

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5416

European-Non Finnish (NFE) AF: 9.01e-7 AC: 1 AN: 1109456

Other (OTH) AF: 0.00 AC: 0 AN: 59996

GnomAD4 genome Cov.: 34

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	0.079
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	14
DANN	Benign	0.67
DEOGEN2	Benign	0.062	T
Eigen	Benign	-0.86
Eigen_PC	Benign	-0.76
FATHMM_MKL	Benign	0.73	D
M_CAP	Benign	0.020	T
MetaRNN	Benign	0.080	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.92	L
PhyloP100		1.5
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-0.16	N
REVEL	Benign	0.037
Sift	Benign	0.75	T
Sift4G	Benign	0.95	T
Polyphen		0.074	B
Vest4		0.18
MutPred		0.40		Loss of helix (P = 0.0626)
MVP		0.33
ClinPred		0.17	T
GERP RS		2.9
PromoterAI		0.044	Neutral
Varity_R		0.054
gMVP		0.10
Mutation Taster		=94/6	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

hg19: chr1-2408145;