chr20-41164170-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PP3_Strong

The NM_002660.3(PLCG1):ā€‹c.1186A>Cā€‹(p.Thr396Pro) variant causes a missense change involving the alteration of a conserved nucleotide. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: š‘“ 0.00043 ( 0 hom., cov: 31)
Exomes š‘“: 0.000020 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

PLCG1
NM_002660.3 missense

Scores

10
8
1

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.52
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PP3
MetaRNN computational evidence supports a deleterious effect, 0.953

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PLCG1NM_002660.3 linkc.1186A>C p.Thr396Pro missense_variant Exon 12 of 32 ENST00000685551.1 NP_002651.2 P19174-2Q4LE43Q9UFY1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
PLCG1ENST00000685551.1 linkc.1186A>C p.Thr396Pro missense_variant Exon 12 of 32 NM_002660.3 ENSP00000508698.1 P19174-2
PLCG1ENST00000373271.5 linkc.1186A>C p.Thr396Pro missense_variant Exon 12 of 32 1 ENSP00000362368.1 P19174-1
PLCG1ENST00000244007.7 linkc.1186A>C p.Thr396Pro missense_variant Exon 13 of 33 5 ENSP00000244007.3 P19174-2

Frequencies

GnomAD3 genomes
AF:
0.00
AC:
67
AN:
151740
Hom.:
0
Cov.:
31
FAILED QC
Gnomad AFR
AF:
0.000218
Gnomad AMI
AF:
0.00110
Gnomad AMR
AF:
0.000459
Gnomad ASJ
AF:
0.000289
Gnomad EAS
AF:
0.00176
Gnomad SAS
AF:
0.00314
Gnomad FIN
AF:
0.000379
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000309
Gnomad OTH
AF:
0.00
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
AF:
0.0000199
AC:
29
AN:
1458612
Hom.:
0
Cov.:
32
AF XY:
0.0000207
AC XY:
15
AN XY:
725654
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.0000384
Gnomad4 EAS exome
AF:
0.0000253
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.0000376
Gnomad4 NFE exome
AF:
0.0000198
Gnomad4 OTH exome
AF:
0.0000332
GnomAD4 genome
Data not reliable, filtered out with message: AS_VQSR
AF:
0.000435
AC:
66
AN:
151862
Hom.:
0
Cov.:
31
AF XY:
0.000431
AC XY:
32
AN XY:
74246
show subpopulations
Gnomad4 AFR
AF:
0.000193
Gnomad4 AMR
AF:
0.000458
Gnomad4 ASJ
AF:
0.000289
Gnomad4 EAS
AF:
0.00176
Gnomad4 SAS
AF:
0.00314
Gnomad4 FIN
AF:
0.000379
Gnomad4 NFE
AF:
0.000309
Gnomad4 OTH
AF:
0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.99
BayesDel_addAF
Pathogenic
0.36
D
BayesDel_noAF
Pathogenic
0.28
CADD
Pathogenic
28
DANN
Uncertain
0.99
DEOGEN2
Pathogenic
0.93
.;D
Eigen
Uncertain
0.60
Eigen_PC
Uncertain
0.62
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Uncertain
0.94
D;D
M_CAP
Uncertain
0.10
D
MetaRNN
Pathogenic
0.95
D;D
MetaSVM
Uncertain
-0.13
T
MutationAssessor
Pathogenic
3.7
H;H
PrimateAI
Pathogenic
0.79
T
PROVEAN
Pathogenic
-4.5
D;D
REVEL
Pathogenic
0.78
Sift
Uncertain
0.0040
D;D
Sift4G
Uncertain
0.056
T;T
Polyphen
0.47
P;P
Vest4
0.79
MutPred
0.84
Gain of methylation at K398 (P = 0.11);Gain of methylation at K398 (P = 0.11);
MVP
0.90
ClinPred
0.98
D
GERP RS
5.3
Varity_R
0.80
gMVP
0.94

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
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: rs779874773; hg19: chr20-39792810; API