2-197805271-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_006226.4(PLCL1):​c.172C>A​(p.Pro58Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000329 in 152,164 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

PLCL1
NM_006226.4 missense

Scores

1
1
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.892
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.06812394).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PLCL1NM_006226.4 linkc.172C>A p.Pro58Thr missense_variant Exon 1 of 6 ENST00000428675.6 NP_006217.3 Q15111-1
PLCL1XM_005246643.5 linkc.-5034C>A upstream_gene_variant XP_005246700.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
PLCL1ENST00000428675.6 linkc.172C>A p.Pro58Thr missense_variant Exon 1 of 6 1 NM_006226.4 ENSP00000402861.1 Q15111-1
PLCL1ENST00000435320.1 linkn.172C>A non_coding_transcript_exon_variant Exon 1 of 7 2 ENSP00000410488.1 F8WAR2

Frequencies

GnomAD3 genomes
AF:
0.0000329
AC:
5
AN:
152164
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000327
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
0.00
AC:
0
AN:
1128452
Hom.:
0
Cov.:
33
AF XY:
0.00
AC XY:
0
AN XY:
538810
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000329
AC:
5
AN:
152164
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
74346
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.000327
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000264

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Feb 07, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.172C>A (p.P58T) alteration is located in exon 1 (coding exon 1) of the PLCL1 gene. This alteration results from a C to A substitution at nucleotide position 172, causing the proline (P) at amino acid position 58 to be replaced by a threonine (T). 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
0.058
BayesDel_addAF
Benign
-0.29
T
BayesDel_noAF
Benign
-0.66
CADD
Benign
17
DANN
Uncertain
0.98
DEOGEN2
Benign
0.041
T
Eigen
Benign
-0.91
Eigen_PC
Benign
-0.86
FATHMM_MKL
Benign
0.14
N
LIST_S2
Benign
0.52
T
M_CAP
Benign
0.026
D
MetaRNN
Benign
0.068
T
MetaSVM
Benign
-0.96
T
MutationAssessor
Benign
1.0
L
PrimateAI
Pathogenic
0.80
T
PROVEAN
Benign
0.12
N
REVEL
Benign
0.023
Sift
Benign
0.033
D
Sift4G
Benign
0.33
T
Polyphen
0.0
B
Vest4
0.11
MutPred
0.19
Gain of phosphorylation at P58 (P = 0.0227);
MVP
0.072
MPC
0.35
ClinPred
0.055
T
GERP RS
2.0
Varity_R
0.038
gMVP
0.26

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1448021182; hg19: chr2-198669995; API