1-153341637-G-T

Variant names:

• chr1-153341637-G-T
• rs73014502
• NM_020393.4:c.615C>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_020393.4(PGLYRP4):​c.615C>A​(p.Ser205Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000556 in 1,612,322 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S205C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.00035 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00058 (1 hom.)
• Consequence: PGLYRP4 NM_020393.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.93
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.015330762).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020393.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PGLYRP4	NM_020393.4	MANE Select	c.615C>A	p.Ser205Arg	missense	Exon 6 of 9	NP_065126.2	Q96LB8-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PGLYRP4	ENST00000359650.10	TSL:1 MANE Select	c.615C>A	p.Ser205Arg	missense	Exon 6 of 9	ENSP00000352672.5	Q96LB8-1
	PGLYRP4	ENST00000368739.3	TSL:5	c.603C>A	p.Ser201Arg	missense	Exon 6 of 9	ENSP00000357728.3	Q96LB8-2

Frequencies

GnomAD3 genomes AF: 0.000348 AC: 53 AN: 152240 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00198

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000470

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000315 AC: 79 AN: 250532 AF XY: 0.000347

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 FIN exome AF: 0.00121

Gnomad NFE exome AF: 0.000433

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000577 AC: 843 AN: 1459964 Hom.: 1 Cov.: 29 AF XY: 0.000549 AC XY: 399 AN XY: 726304

African (AFR) AF: 0.000120 AC: 4 AN: 33432

American (AMR) AF: 0.0000448 AC: 2 AN: 44672

Ashkenazi Jewish (ASJ) AF: 0.0000384 AC: 1 AN: 26072

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.000221 AC: 19 AN: 86140

European-Finnish (FIN) AF: 0.00111 AC: 59 AN: 53348

Middle Eastern (MID) AF: 0.000418 AC: 2 AN: 4780

European-Non Finnish (NFE) AF: 0.000661 AC: 735 AN: 1111558

Other (OTH) AF: 0.000348 AC: 21 AN: 60264

GnomAD4 genome AF: 0.000348 AC: 53 AN: 152358 Hom.: 0 Cov.: 33 AF XY: 0.000416 AC XY: 31 AN XY: 74506

African (AFR) AF: 0.00 AC: 0 AN: 41588

American (AMR) AF: 0.00 AC: 0 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00198 AC: 21 AN: 10628

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000470 AC: 32 AN: 68036

Other (OTH) AF: 0.00 AC: 0 AN: 2116

Alfa AF: 0.0000536 Hom.: 0

Bravo AF: 0.000196

TwinsUK AF: 0.00108 AC: 4

ALSPAC AF: 0.000259 AC: 1

ExAC AF: 0.000288 AC: 35

EpiCase AF: 0.000382

EpiControl AF: 0.000297

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.54	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	0.044
DANN	Benign	0.36
DEOGEN2	Benign	0.031	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.0045	N
LIST_S2	Benign	0.31	T
M_CAP	Benign	0.0020	T
MetaRNN	Benign	0.015	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	0.81	L
PhyloP100		-1.9
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-0.37	N
REVEL	Benign	0.0070
Sift	Benign	0.53	T
Sift4G	Benign	0.52	T
Polyphen		0.0040	B
Vest4		0.19
MutPred		0.51		Gain of MoRF binding (P = 0.0134)
MVP		0.14
MPC		0.057
ClinPred		0.013	T
GERP RS		-4.7
Varity_R		0.068
gMVP		0.30
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs73014502; hg19: chr1-153314113;