20-8132679-G-C

Variant names:

• chr20-8132679-G-C
• NM_015192.4:c.28G>C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_015192.4(PLCB1):​c.28G>C​(p.Ala10Pro) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PLCB1 NM_015192.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 8.49

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLCB1	NM_015192.4	c.28G>C	p.Ala10Pro	missense_variant	Exon 1 of 32	ENST00000338037.11	NP_056007.1
PLCB1	NM_182734.3	c.28G>C	p.Ala10Pro	missense_variant	Exon 1 of 33		NP_877398.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLCB1	ENST00000338037.11	c.28G>C	p.Ala10Pro	missense_variant	Exon 1 of 32	1	NM_015192.4	ENSP00000338185.6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.84
BayesDel_addAF	Uncertain	0.075	D
BayesDel_noAF	Benign	-0.13
CADD	Pathogenic	30
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.47	.;T;.;.;.
Eigen	Pathogenic	0.72
Eigen_PC	Pathogenic	0.71
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.96	.;D;D;D;D
M_CAP	Pathogenic	0.52	D
MetaRNN	Uncertain	0.61	D;D;D;D;D
MetaSVM	Benign	-0.59	T
MutationAssessor	Uncertain	2.4	M;M;.;.;M
PrimateAI	Pathogenic	0.89	D
PROVEAN	Benign	-1.6	N;N;.;.;N
REVEL	Benign	0.25
Sift	Uncertain	0.0090	D;D;.;.;D
Sift4G	Benign	0.080	T;T;D;D;T
Polyphen		1.0	D;D;.;.;D
Vest4		0.61
MutPred		0.59		Gain of disorder (P = 0.0426);Gain of disorder (P = 0.0426);Gain of disorder (P = 0.0426);Gain of disorder (P = 0.0426);Gain of disorder (P = 0.0426);
MVP		0.33
MPC		0.13
ClinPred		0.97	D
GERP RS		4.8
Varity_R		0.62
gMVP		0.78

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: chr20-8113326;