2-197805143-A-C

Variant names:

• chr2-197805143-A-C
• NM_006226.4:c.44A>C

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.44A>C​(p.Asp15Ala) 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. 13/22 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)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PLCL1 NM_006226.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.50
• Publications: 0 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]

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=0.15137285).

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.44A>C	p.Asp15Ala	missense	Exon 1 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.44A>C	p.Asp15Ala	missense	Exon 1 of 6	ENSP00000402861.1	Q15111-1
	PLCL1	ENST00000435320.1	TSL:2	n.44A>C		non_coding_transcript_exon	Exon 1 of 7	ENSP00000410488.1	F8WAR2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1158784 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 557764

African (AFR) AF: 0.00 AC: 0 AN: 23172

American (AMR) AF: 0.00 AC: 0 AN: 8666

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15786

East Asian (EAS) AF: 0.00 AC: 0 AN: 26704

South Asian (SAS) AF: 0.00 AC: 0 AN: 41012

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 26298

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3190

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 966808

Other (OTH) AF: 0.00 AC: 0 AN: 47148

GnomAD4 genome Cov.: 33

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	0.046
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	19
DANN	Benign	0.96
DEOGEN2	Benign	0.036	T
Eigen	Benign	-0.59
Eigen_PC	Benign	-0.46
FATHMM_MKL	Benign	0.69	D
LIST_S2	Benign	0.39	T
M_CAP	Uncertain	0.21	D
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PhyloP100		4.5
PrimateAI	Pathogenic	0.89	D
PROVEAN	Benign	0.020	N
REVEL	Benign	0.091
Sift	Benign	0.060	T
Sift4G	Benign	0.17	T
Polyphen		0.0020	B
Vest4		0.25
MutPred		0.14		Loss of solvent accessibility (P = 0.0249)
MVP		0.14
MPC		0.39
ClinPred		0.17	T
GERP RS		4.0
Varity_R		0.082
gMVP		0.19
Mutation Taster		=97/3	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: chr2-198669867;