1-153341637-G-C

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_020393.4(PGLYRP4):​c.615C>G​(p.Ser205Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000513 in 1,612,330 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 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 0.0029 (5 hom., cov: 33)
  • Exomes 𝑓: 0.00027 (3 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: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0037300885).
• BS2: High Homozygotes in GnomAd4 at 5 AR gene

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>G	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>G	p.Ser205Arg	missense	Exon 6 of 9	ENSP00000352672.5	Q96LB8-1
	PGLYRP4	ENST00000368739.3	TSL:5	c.603C>G	p.Ser201Arg	missense	Exon 6 of 9	ENSP00000357728.3	Q96LB8-2

Frequencies

GnomAD3 genomes AF: 0.00282 AC: 429 AN: 152240 Hom.: 2 Cov.: 33

Gnomad AFR AF: 0.00986

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000981

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00143

GnomAD2 exomes AF: 0.000663 AC: 166 AN: 250532 AF XY: 0.000391

Gnomad AFR exome AF: 0.00904

Gnomad AMR exome AF: 0.000492

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000884

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000266 AC: 389 AN: 1459972 Hom.: 3 Cov.: 29 AF XY: 0.000219 AC XY: 159 AN XY: 726308

African (AFR) AF: 0.00924 AC: 309 AN: 33428

American (AMR) AF: 0.000515 AC: 23 AN: 44672

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26072

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

South Asian (SAS) AF: 0.0000232 AC: 2 AN: 86140

European-Finnish (FIN) AF: 0.0000187 AC: 1 AN: 53348

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4780

European-Non Finnish (NFE) AF: 0.00000810 AC: 9 AN: 1111570

Other (OTH) AF: 0.000747 AC: 45 AN: 60264

GnomAD4 genome AF: 0.00287 AC: 438 AN: 152358 Hom.: 5 Cov.: 33 AF XY: 0.00278 AC XY: 207 AN XY: 74506

African (AFR) AF: 0.0101 AC: 418 AN: 41588

American (AMR) AF: 0.000980 AC: 15 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: 0.00 AC: 0 AN: 10628

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

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68036

Other (OTH) AF: 0.00142 AC: 3 AN: 2116

Alfa AF: 0.000129 Hom.: 0

Bravo AF: 0.00309

ESP6500AA AF: 0.00840 AC: 37

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.000840 AC: 102

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	-0.65	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	0.044
DANN	Benign	0.38
DEOGEN2	Benign	0.031	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.0055	N
LIST_S2	Benign	0.31	T
MetaRNN	Benign	0.0037	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	0.0090
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		0.0026	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)		0.040		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;