rs200893556

Variant names:

• chr12-11353363-C-G
• rs200893556
• ENST00000500254.6:c.341G>C

Your query was ambiguous. Multiple possible variants found:

• chr12-11353363-C-G
• chr12-11353363-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The ENST00000500254.6(PRB1):​c.341G>C​(p.Gly114Ala) 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. 12/18 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. G114E) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 17)
• Consequence: PRB1 ENST00000500254.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.759

Genes affected

PRB1 (HGNC:9337): (proline rich protein BstNI subfamily 1) Predicted to be located in extracellular region. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09289998).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRB1	NR_160307.2	n.778G>C		non_coding_transcript_exon_variant	Exon 3 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRB1	ENST00000500254.6	c.341G>C	p.Gly114Ala	missense_variant	Exon 4 of 5	1		ENSP00000420826.2
PRB1	ENST00000545626.5	c.314-33G>C		intron_variant	Intron 3 of 4	1		ENSP00000444249.1
PRB1	ENST00000240636.10	n.*284G>C		non_coding_transcript_exon_variant	Exon 3 of 4	1		ENSP00000485971.1
PRB1	ENST00000240636.10	n.*284G>C		3_prime_UTR_variant	Exon 3 of 4	1		ENSP00000485971.1

Frequencies

GnomAD3 genomes Cov.: 17

GnomAD4 exome Cov.: 54

GnomAD4 genome Cov.: 17

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.73
CADD	Benign	4.3
DANN	Benign	0.28
DEOGEN2	Benign	0.099	.;T
Eigen	Benign	-0.97
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.0022	N
M_CAP	Benign	0.00056	T
MetaRNN	Benign	0.093	T;T
MetaSVM	Benign	-1.0	T
PrimateAI	Benign	0.38	T
PROVEAN	Uncertain	-2.5	D;.
REVEL	Benign	0.022
Sift	Pathogenic	0.0	D;.
Sift4G	Benign	0.20	T;T
Vest4		0.14
MutPred		0.31		Gain of catalytic residue at P111 (P = 5e-04);.;
MVP		0.072
MPC		0.058
ClinPred		0.10	T
GERP RS		-2.4
gMVP		0.034

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

LitVar

Other links and lift over

dbSNP: rs200893556; hg19: chr12-11506297;