chr14-103739853-G-C

Variant names:

• chr14-103739853-G-C
• rs368881952
• NM_015316.3:c.2563C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_015316.3(PPP1R13B):​c.2563C>G​(p.Pro855Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P855S) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: PPP1R13B NM_015316.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.52
• Publications: 0 publications found

Genes affected

PPP1R13B (HGNC:14950): (protein phosphatase 1 regulatory subunit 13B) This gene encodes a member of the ASPP (apoptosis-stimulating protein of p53) family of p53 interacting proteins. The protein contains four ankyrin repeats and an SH3 domain involved in protein-protein interactions. ASPP proteins are required for the induction of apoptosis by p53-family proteins. They promote DNA binding and transactivation of p53-family proteins on the promoters of proapoptotic genes. Expression of this gene is regulated by the E2F transcription factor. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.103238195).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPP1R13B	NM_015316.3	c.2563C>G	p.Pro855Ala	missense_variant	Exon 12 of 17	ENST00000202556.14	NP_056131.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPP1R13B	ENST00000202556.14	c.2563C>G	p.Pro855Ala	missense_variant	Exon 12 of 17	1	NM_015316.3	ENSP00000202556.9

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ESP6500AA AF: 0.000244 AC: 1

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.00000827 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.052
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	11
DANN	Benign	0.68
DEOGEN2	Benign	0.26	.;T
Eigen	Benign	-0.51
Eigen_PC	Benign	-0.50
FATHMM_MKL	Benign	0.46	N
LIST_S2	Benign	0.58	T;T
M_CAP	Benign	0.022	T
MetaRNN	Benign	0.10	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.2	.;M
PhyloP100		2.5
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-2.0	.;N
REVEL	Benign	0.031
Sift	Benign	0.76	.;T
Sift4G	Benign	0.74	.;T
Polyphen		0.20	.;B
Vest4		0.14
MVP		0.65
MPC		0.38
ClinPred		0.074	T
GERP RS		2.2
Varity_R		0.044
gMVP		0.28
Mutation Taster		=95/5	polymorphism

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

Other links and lift over

dbSNP: rs368881952; hg19: chr14-104206190;