2-198084350-C-G

Variant names:

• chr2-198084350-C-G
• rs61752178
• NM_006226.4:c.833C>G

Variant summary

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

The NM_006226.4(PLCL1):​c.833C>G​(p.Ala278Gly) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A278V) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PLCL1 NM_006226.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.95
• Publications: 13 publications found

Genes affected

PLCL1 (HGNC:9063): (phospholipase C like 1 (inactive)) Predicted to enable phospholipase C activity. Predicted to be involved in negative regulation of cold-induced thermogenesis and phosphatidylinositol-mediated signaling. Predicted to act upstream of or within several processes, including gamma-aminobutyric acid signaling pathway; regulation of GABAergic synaptic transmission; and regulation of peptidyl-serine phosphorylation. Predicted to be located in cytoplasm and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000305132 (HGNC:):

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=0.19744924).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006226.4. 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
	PLCL1	NM_006226.4	MANE Select	c.833C>G	p.Ala278Gly	missense	Exon 2 of 6	NP_006217.3	Q15111-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLCL1	ENST00000428675.6	TSL:1 MANE Select	c.833C>G	p.Ala278Gly	missense	Exon 2 of 6	ENSP00000402861.1	Q15111-1
	PLCL1	ENST00000487695.6	TSL:5	c.611C>G	p.Ala204Gly	missense	Exon 2 of 6	ENSP00000457588.1	H3BUD4
	PLCL1	ENST00000435320.1	TSL:2	n.*605C>G		non_coding_transcript_exon	Exon 3 of 7	ENSP00000410488.1	F8WAR2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 2

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.060	T
Eigen	Benign	0.11
Eigen_PC	Uncertain	0.30
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Benign	0.65	T
M_CAP	Benign	0.0095	T
MetaRNN	Benign	0.20	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.2	L
PhyloP100		4.9
PrimateAI	Benign	0.41	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.086
Sift	Benign	0.24	T
Sift4G	Benign	0.30	T
Polyphen		0.0010	B
Vest4		0.11
MutPred		0.33		Loss of stability (P = 0.0533)
MVP		0.53
MPC		0.32
ClinPred		0.68	D
GERP RS		5.7
Varity_R		0.14
gMVP		0.13
Mutation Taster		=82/18	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: rs61752178; hg19: chr2-198949074;