rs3813135

Positions:

• chr19-15476534-T-A
• chr19-15476534-T-C
• chr19-15476534-T-G

Variant summary

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

The NM_052890.4(PGLYRP2):​c.136A>T​(p.Thr46Ser) 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. 15/21 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. T46A) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PGLYRP2 NM_052890.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0330

Genes affected

PGLYRP2 (HGNC:30013): (peptidoglycan recognition protein 2) This gene encodes a peptidoglycan recognition protein, which belongs to the N-acetylmuramoyl-L-alanine amidase 2 family. This protein hydrolyzes the link between N-acetylmuramoyl residues and L-amino acid residues in bacterial cell wall glycopeptides, and thus may play a scavenger role by digesting biologically active peptidoglycan into biologically inactive fragments. [provided by RefSeq, Sep 2011]

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=0.07347143).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PGLYRP2	NM_052890.4	c.136A>T	p.Thr46Ser	missense_variant	2/5	ENST00000340880.5	NP_443122.3
PGLYRP2	NM_001363546.1	c.136A>T	p.Thr46Ser	missense_variant	2/4		NP_001350475.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PGLYRP2	ENST00000340880.5	c.136A>T	p.Thr46Ser	missense_variant	2/5	1	NM_052890.4	ENSP00000345968	P2
PGLYRP2	ENST00000292609.8	c.136A>T	p.Thr46Ser	missense_variant	2/4	1		ENSP00000292609	A2
PGLYRP2	ENST00000601792.1	c.244A>T	p.Thr82Ser	missense_variant	4/4	4		ENSP00000472856
PGLYRP2	ENST00000594637.1	c.136A>T	p.Thr46Ser	missense_variant	3/3	4		ENSP00000470112

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 58

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.085
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.75
CADD	Benign	2.2
DANN	Benign	0.68
DEOGEN2	Benign	0.039	.;T;T;T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.040	N
LIST_S2	Benign	0.37	T;T;T;T
M_CAP	Benign	0.0070	T
MetaRNN	Benign	0.073	T;T;T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.34	N;N;.;.
MutationTaster	Benign	1.0	P;P
PrimateAI	Benign	0.28	T
PROVEAN	Benign	0.27	N;N;.;.
REVEL	Benign	0.025
Sift	Uncertain	0.0050	D;D;.;.
Sift4G	Benign	0.36	T;T;T;.
Polyphen		0.0010	B;B;.;.
Vest4		0.085
MutPred		0.15		Gain of disorder (P = 0.0437);Gain of disorder (P = 0.0437);.;Gain of disorder (P = 0.0437);
MVP		0.19
MPC		0.15
ClinPred		0.11	T
GERP RS		2.0
Varity_R		0.043
gMVP		0.20

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: rs3813135; hg19: chr19-15587345;