19-46019296-G-A

Position:

• chr19-46019296-G-A

Variant summary

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

The NM_005091.3(PGLYRP1):​c.533C>T​(p.Ser178Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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)
• Consequence: PGLYRP1 NM_005091.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.89

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:33629): (coiled-coil domain containing 61) Enables identical protein binding activity and microtubule binding activity. Involved in centriole assembly and mitotic spindle assembly. Located in centriolar satellite and ciliary basal body. Part of centriolar subdistal appendage. [provided by Alliance of Genome Resources, Apr 2022]

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, 0.793

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PGLYRP1	NM_005091.3	c.533C>T	p.Ser178Phe	missense_variant	3/3	ENST00000008938.5	NP_005082.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PGLYRP1	ENST00000008938.5	c.533C>T	p.Ser178Phe	missense_variant	3/3	1	NM_005091.3	ENSP00000008938.3
CCDC61	ENST00000601763.1	n.54+864G>A		intron_variant		3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 31

Bravo AF: 0.00000378

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

Oct 29, 2024

The c.533C>T (p.S178F) alteration is located in exon 3 (coding exon 3) of the PGLYRP1 gene. This alteration results from a C to T substitution at nucleotide position 533, causing the serine (S) at amino acid position 178 to be replaced by a phenylalanine (F). 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	Pathogenic	0.93
BayesDel_addAF	Benign	-0.035	T
BayesDel_noAF	Benign	-0.29
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.33	T
Eigen	Uncertain	0.42
Eigen_PC	Uncertain	0.24
FATHMM_MKL	Uncertain	0.78	D
LIST_S2	Benign	0.82	T
M_CAP	Benign	0.018	T
MetaRNN	Pathogenic	0.79	D
MetaSVM	Benign	-0.74	T
MutationAssessor	Pathogenic	3.5	H
PrimateAI	Benign	0.44	T
PROVEAN	Uncertain	-4.1	D
REVEL	Benign	0.28
Sift	Benign	0.032	D
Sift4G	Uncertain	0.0060	D
Polyphen		1.0	D
Vest4		0.40
MutPred		0.80		Loss of disorder (P = 0.0071);
MVP		0.64
MPC		0.93
ClinPred		0.99	D
GERP RS		3.3
Varity_R		0.40
gMVP		0.89

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: rs1969016973; hg19: chr19-46522554;