chr19-46019589-C-T

Position:

• chr19-46019589-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_005091.3(PGLYRP1):​c.346G>A​(p.Ala116Thr) variant causes a missense change. The variant allele was found at a frequency of 0.0000356 in 1,461,744 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.000036 (0 hom.)
• Consequence: PGLYRP1 NM_005091.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.64

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]

CCDC61 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.765

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PGLYRP1	NM_005091.3	c.346G>A	p.Ala116Thr	missense_variant	2/3	ENST00000008938.5	NP_005082.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PGLYRP1	ENST00000008938.5	c.346G>A	p.Ala116Thr	missense_variant	2/3	1	NM_005091.3	ENSP00000008938.3
CCDC61	ENST00000601763.1	n.54+1157C>T		intron_variant		3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.0000356 AC: 52 AN: 1461744 Hom.: 0 Cov.: 33 AF XY: 0.0000330 AC XY: 24 AN XY: 727184

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: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000450

Gnomad4 OTH exome AF: 0.0000331

GnomAD4 genome Cov.: 31

Alfa AF: 0.0000741 Hom.: 0

Bravo AF: 0.00000378

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.00000824 AC: 1

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

Feb 08, 2023

The c.346G>A (p.A116T) alteration is located in exon 2 (coding exon 2) of the PGLYRP1 gene. This alteration results from a G to A substitution at nucleotide position 346, causing the alanine (A) at amino acid position 116 to be replaced by a threonine (T). 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	0.27
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	19
DANN	Uncertain	1.0
DEOGEN2	Benign	0.30	T
Eigen	Uncertain	0.31
Eigen_PC	Benign	0.13
FATHMM_MKL	Benign	0.36	N
LIST_S2	Benign	0.48	T
M_CAP	Benign	0.0078	T
MetaRNN	Pathogenic	0.76	D
MetaSVM	Benign	-0.94	T
MutationAssessor	Pathogenic	2.9	M
PrimateAI	Benign	0.31	T
PROVEAN	Uncertain	-2.4	N
REVEL	Benign	0.24
Sift	Uncertain	0.012	D
Sift4G	Uncertain	0.010	D
Polyphen		0.98	D
Vest4		0.37
MVP		0.39
MPC		0.78
ClinPred		0.83	D
GERP RS		5.0
Varity_R		0.19
gMVP		0.79

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: rs374335177; hg19: chr19-46522847; COSMIC: COSV50517528; COSMIC: COSV50517528;