Variant 1-153340507-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_020393.4(PGLYRP4):c.698C>T(p.Ala233Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000385 in 1,614,126 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00027 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00040 ( 1 hom. )

Consequence

PGLYRP4
NM_020393.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.36

Variant links:

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 links:

PGLYRP4 (HGNC:):

PGLYRP4 links:

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ACMG classification

Classification made for transcript

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=0.0406895).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PGLYRP4	NM_020393.4 linkuse as main transcript	c.698C>T	p.Ala233Val	missense_variant	7/9	ENST00000359650.10	NP_065126.2	Q96LB8-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PGLYRP4	ENST00000359650.10 linkuse as main transcript	c.698C>T	p.Ala233Val	missense_variant	7/9	1	NM_020393.4	ENSP00000352672.5		Q96LB8-1
PGLYRP4	ENST00000368739.3 linkuse as main transcript	c.686C>T	p.Ala229Val	missense_variant	7/9	5		ENSP00000357728.3		Q96LB8-2

Frequencies

GnomAD3 genomes

AF:

0.000269

AC:

AN:

152140

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000314

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.0000942

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000323

Gnomad OTH

AF:

0.000479

GnomAD3 exomes

AF:

0.000549

AC:

138

AN:

251234

Hom.:

AF XY:

0.000486

AC XY:

AN XY:

135772

show subpopulations

Gnomad AFR exome

AF:

0.000369

Gnomad AMR exome

AF:

0.000463

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000786

Gnomad NFE exome

AF:

0.000819

Gnomad OTH exome

AF:

0.000815

GnomAD4 exome

AF:

0.000397

AC:

581

AN:

1461868

Hom.:

Cov.:

AF XY:

0.000392

AC XY:

285

AN XY:

727232

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.000470

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00155

Gnomad4 NFE exome

AF:

0.000398

Gnomad4 OTH exome

AF:

0.000530

GnomAD4 genome

AF:

0.000269

AC:

AN:

152258

Hom.:

Cov.:

AF XY:

0.000242

AC XY:

AN XY:

74444

show subpopulations

Gnomad4 AFR

AF:

0.000313

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.0000942

Gnomad4 NFE

AF:

0.000323

Gnomad4 OTH

AF:

0.000474

Alfa

AF:

0.000362

Hom.:

Bravo

AF:

0.000340

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.000465

AC:

ExAC

AF:

0.000618

AC:

EpiCase

AF:

0.000436

EpiControl

AF:

0.000771

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 29, 2021

The c.698C>T (p.A233V) alteration is located in exon 7 (coding exon 6) of the PGLYRP4 gene. This alteration results from a C to T substitution at nucleotide position 698, causing the alanine (A) at amino acid position 233 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

0.15

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.52

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.025

T;.

Eigen

Benign

-0.21

Eigen_PC

Benign

-0.25

FATHMM_MKL

Benign

0.65

LIST_S2

Benign

0.77

T;T

M_CAP

Benign

0.0042

MetaRNN

Benign

0.041

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.65

N;.

PrimateAI

Uncertain

0.50

PROVEAN

Benign

-0.29

N;N

REVEL

Benign

0.14

Sift

Benign

0.64

T;T

Sift4G

Benign

0.42

T;T

Polyphen

0.99

D;D

Vest4

0.17

MVP

0.24

MPC

0.33

ClinPred

0.021

GERP RS

3.6

Varity_R

0.26

gMVP

0.28

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over