chr19-46022834-G-T

Position:

• chr19-46022834-G-T

Variant summary

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

The NM_005091.3(PGLYRP1):​c.188C>A​(p.Ala63Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: PGLYRP1 NM_005091.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.18

Genes affected

PGLYRP1 (HGNC:8904): (peptidoglycan recognition protein 1) Enables peptidoglycan binding activity and peptidoglycan immune receptor activity. Involved in antimicrobial humoral immune response mediated by antimicrobial peptide; killing of cells of other organism; and response to bacterium. Located in extracellular exosome. [provided by Alliance of Genome Resources, Apr 2022]

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/exons	MANE	UniProt
PGLYRP1	NM_005091.3	c.188C>A	p.Ala63Glu	missense_variant	1/3	ENST00000008938.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PGLYRP1	ENST00000008938.5	c.188C>A	p.Ala63Glu	missense_variant	1/3	1	NM_005091.3	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

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 06, 2022

The c.188C>A (p.A63E) alteration is located in exon 1 (coding exon 1) of the PGLYRP1 gene. This alteration results from a C to A substitution at nucleotide position 188, causing the alanine (A) at amino acid position 63 to be replaced by a glutamic acid (E). 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	Pathogenic	0.61
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	18
DANN	Uncertain	0.98
DEOGEN2	Benign	0.23	T
Eigen	Benign	0.17
Eigen_PC	Benign	0.10
FATHMM_MKL	Benign	0.74	D
LIST_S2	Benign	0.63	T
M_CAP	Benign	0.020	T
MetaRNN	Uncertain	0.46	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Pathogenic	3.0	M
MutationTaster	Benign	0.74	D
PrimateAI	Benign	0.42	T
PROVEAN	Uncertain	-4.3	D
REVEL	Benign	0.12
Sift	Uncertain	0.027	D
Sift4G	Benign	0.079	T
Polyphen		0.86	P
Vest4		0.34
MutPred		0.73		Gain of disorder (P = 0.0299);
MVP		0.52
MPC		0.78
ClinPred		0.96	D
GERP RS		3.5
Varity_R		0.60
gMVP		0.90

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: chr19-46526092;