20-41160141-A-G
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 3P and 2B. PM1PP2BP4_Moderate
The NM_002660.3(PLCG1):c.500A>G(p.Asn167Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000116 in 1,461,772 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: not found (cov: 32)
Exomes 𝑓: 0.000012 ( 0 hom. )
Consequence
PLCG1
NM_002660.3 missense
NM_002660.3 missense
Scores
4
14
Clinical Significance
Conservation
PhyloP100: 5.57
Genes affected
PLCG1 (HGNC:9065): (phospholipase C gamma 1) The protein encoded by this gene catalyzes the formation of inositol 1,4,5-trisphosphate and diacylglycerol from phosphatidylinositol 4,5-bisphosphate. This reaction uses calcium as a cofactor and plays an important role in the intracellular transduction of receptor-mediated tyrosine kinase activators. For example, when activated by SRC, the encoded protein causes the Ras guanine nucleotide exchange factor RasGRP1 to translocate to the Golgi, where it activates Ras. Also, this protein has been shown to be a major substrate for heparin-binding growth factor 1 (acidic fibroblast growth factor)-activated tyrosine kinase. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 1 ACMG points.
PM1
?
In a binding_site (size 0) in uniprot entity PLCG1_HUMAN
PP2
?
Missense variant where missense usually causes diseases, PLCG1
BP4
?
Computational evidence support a benign effect (MetaRNN=0.23926133).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PLCG1 | NM_002660.3 | c.500A>G | p.Asn167Ser | missense_variant | 4/32 | ENST00000685551.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PLCG1 | ENST00000685551.1 | c.500A>G | p.Asn167Ser | missense_variant | 4/32 | NM_002660.3 | P3 | ||
PLCG1 | ENST00000373271.5 | c.500A>G | p.Asn167Ser | missense_variant | 4/32 | 1 | A1 | ||
PLCG1 | ENST00000244007.7 | c.500A>G | p.Asn167Ser | missense_variant | 5/33 | 5 | P3 | ||
PLCG1 | ENST00000483646.2 | n.410A>G | non_coding_transcript_exon_variant | 4/6 | 3 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD4 exome AF: 0.0000116 AC: 17AN: 1461772Hom.: 0 Cov.: 31 AF XY: 0.0000124 AC XY: 9AN XY: 727194
GnomAD4 exome
AF:
AC:
17
AN:
1461772
Hom.:
Cov.:
31
AF XY:
AC XY:
9
AN XY:
727194
Gnomad4 AFR exome
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GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Apr 19, 2023 | The c.500A>G (p.N167S) alteration is located in exon 4 (coding exon 4) of the PLCG1 gene. This alteration results from a A to G substitution at nucleotide position 500, causing the asparagine (N) at amino acid position 167 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Uncertain
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D
M_CAP
Benign
T
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationAssessor
Benign
L;L
MutationTaster
Benign
D;D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N
REVEL
Benign
Sift
Benign
T;T
Sift4G
Benign
T;T
Polyphen
0.0
.;B
Vest4
MutPred
Gain of phosphorylation at N167 (P = 0.0117);Gain of phosphorylation at N167 (P = 0.0117);
MVP
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at