20-8697694-G-T

Variant names:

• chr20-8697694-G-T
• NM_015192.4:c.1078G>T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_015192.4(PLCB1):​c.1078G>T​(p.Val360Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,878 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: PLCB1 NM_015192.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.46

Genes affected

PLCB1 (HGNC:15917): (phospholipase C beta 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 many extracellular signals. This gene is activated by two G-protein alpha subunits, alpha-q and alpha-11. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.75

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLCB1	NM_015192.4	c.1078G>T	p.Val360Leu	missense_variant	Exon 11 of 32	ENST00000338037.11	NP_056007.1
PLCB1	NM_182734.3	c.1078G>T	p.Val360Leu	missense_variant	Exon 11 of 33		NP_877398.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLCB1	ENST00000338037.11	c.1078G>T	p.Val360Leu	missense_variant	Exon 11 of 32	1	NM_015192.4	ENSP00000338185.6

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461878 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727244

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: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.56
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.070
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.45	.;.;.;T;.;T;.;T
Eigen	Uncertain	0.57
Eigen_PC	Uncertain	0.63
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.91	D;D;.;D;D;D;D;D
M_CAP	Benign	0.015	T
MetaRNN	Pathogenic	0.75	D;D;D;D;D;D;D;D
MetaSVM	Benign	-0.66	T
MutationAssessor	Benign	1.3	.;.;L;L;L;.;.;.
PrimateAI	Uncertain	0.77	T
PROVEAN	Benign	-2.2	.;.;N;N;N;.;.;.
REVEL	Uncertain	0.33
Sift	Benign	0.036	.;.;D;D;D;.;.;.
Sift4G	Uncertain	0.059	.;T;T;T;T;T;T;T
Polyphen		0.88, 0.86	.;.;P;P;P;.;.;.
Vest4		0.68, 0.68
MutPred		0.81		.;.;Gain of catalytic residue at V360 (P = 0.1519);Gain of catalytic residue at V360 (P = 0.1519);Gain of catalytic residue at V360 (P = 0.1519);.;.;.;
MVP		0.80
MPC		1.9
ClinPred		0.87	D
GERP RS		5.7
Varity_R		0.24
gMVP		0.77

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr20-8678341;