rs3006458

chr1-153347896-T-Achr1-153347896-T-Cchr1-153347896-T-G

Variant summary

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

The NM_020393.4(PGLYRP4):c.37A>T(p.Ile13Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,460,594 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. I13L) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: PGLYRP4 NM_020393.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.186

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]

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=0.0544326).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PGLYRP4	NM_020393.4	c.37A>T	p.Ile13Phe	missense_variant	2/9	ENST00000359650.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PGLYRP4	ENST00000359650.10	c.37A>T	p.Ile13Phe	missense_variant	2/9	1	NM_020393.4	P4
PGLYRP4	ENST00000368739.3	c.37A>T	p.Ile13Phe	missense_variant	2/9	5		A1
PGLYRP4	ENST00000490266.1	n.83A>T		non_coding_transcript_exon_variant	1/3	3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD3 exomes AF: 0.00000399 AC: 1 AN: 250354 Hom.: 0 AF XY: 0.00000739 AC XY: 1 AN XY: 135350

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000328

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1460594 Hom.: 0 Cov.: 38 AF XY: 0.00000275 AC XY: 2 AN XY: 726672

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000348

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.055
BayesDel_addAF	Benign	-0.45	T
BayesDel_noAF	Benign	-0.78
Cadd	Benign	13
Dann	Benign	0.89
DEOGEN2	Benign	0.046	T;.
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.0075	N
LIST_S2	Benign	0.24	T;T
M_CAP	Benign	0.0037	T
MetaRNN	Benign	0.054	T;T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	0.0	N;N
MutationTaster	Benign	1.0	P;P
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-0.96	N;N
REVEL	Benign	0.032
Sift	Benign	0.052	T;T
Sift4G	Uncertain	0.0080	D;D
Polyphen		0.0	B;B
Vest4		0.16
MutPred		0.32		Loss of MoRF binding (P = 0.165);Loss of MoRF binding (P = 0.165);
MVP		0.13
MPC		0.076
ClinPred		0.082	T
GERP RS		-1.1
Varity_R		0.062
gMVP		0.30

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: rs3006458; hg19: chr1-153320372;