1-153337276-G-A

Position:

• chr1-153337276-G-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_020393.4(PGLYRP4):​c.848C>T​(p.Ala283Val) 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. A283T) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PGLYRP4 NM_020393.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -3.74

Genes affected

PGLYRP4 (HGNC:30015): (peptidoglycan recognition protein 4) Summary: This gene encodes a peptidoglycan recognition protein, which belongs to the N-acetylmuramoyl-L-alanine amidase 2 family. These proteins are part of the innate immune system and recognize peptidoglycan, a ubiquitous component of bacterial cell walls. This antimicrobial protein binds to murein peptidoglycans of Gram-positive bacteria. [provided by RefSeq, Oct 2014]

PGLYRP4 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.04058683).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PGLYRP4	NM_020393.4	c.848C>T	p.Ala283Val	missense_variant	8/9	ENST00000359650.10	NP_065126.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PGLYRP4	ENST00000359650.10	c.848C>T	p.Ala283Val	missense_variant	8/9	1	NM_020393.4	ENSP00000352672.5
PGLYRP4	ENST00000368739.3	c.836C>T	p.Ala279Val	missense_variant	8/9	5		ENSP00000357728.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 03, 2024

The c.848C>T (p.A283V) alteration is located in exon 8 (coding exon 7) of the PGLYRP4 gene. This alteration results from a C to T substitution at nucleotide position 848, causing the alanine (A) at amino acid position 283 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.077
BayesDel_addAF	Benign	-0.39	T
BayesDel_noAF	Benign	-0.80
CADD	Benign	0.0070
DANN	Benign	0.87
DEOGEN2	Benign	0.018	T;.
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.0037	N
LIST_S2	Benign	0.045	T;T
M_CAP	Benign	0.0026	T
MetaRNN	Benign	0.041	T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	-0.26	N;.
PrimateAI	Benign	0.21	T
PROVEAN	Benign	-0.12	N;N
REVEL	Benign	0.012
Sift	Benign	0.32	T;T
Sift4G	Benign	0.30	T;T
Polyphen		0.0040	B;B
Vest4		0.13
MutPred		0.45		Loss of sheet (P = 0.302);.;
MVP		0.040
MPC		0.052
ClinPred		0.36	T
GERP RS		-6.4
Varity_R		0.12
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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-153309752;