19-46019381-C-G

Variant names:

• chr19-46019381-C-G
• rs780417589
• NM_005091.3:c.448G>C

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_005091.3(PGLYRP1):​c.448G>C​(p.Gly150Arg) 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 benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G150S) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PGLYRP1 NM_005091.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.690
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.35107267).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005091.3. 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
	PGLYRP1	NM_005091.3	MANE Select	c.448G>C	p.Gly150Arg	missense	Exon 3 of 3	NP_005082.1	O75594

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PGLYRP1	ENST00000008938.5	TSL:1 MANE Select	c.448G>C	p.Gly150Arg	missense	Exon 3 of 3	ENSP00000008938.3	O75594
	CCDC61	ENST00000601763.1	TSL:3	n.54+949C>G		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD2 exomes AF: 0.00000399 AC: 1 AN: 250514 AF XY: 0.00000738

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: 0.00

Gnomad NFE exome AF: 0.00000883

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 6.84e-7 AC: 1 AN: 1461590 Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1 AN XY: 727098

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26122

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

South Asian (SAS) AF: 0.00 AC: 0 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53192

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111974

Other (OTH) AF: 0.00 AC: 0 AN: 60392

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	14
DANN	Uncertain	0.98
DEOGEN2	Benign	0.11	T
Eigen	Benign	-0.74
Eigen_PC	Benign	-0.71
FATHMM_MKL	Benign	0.048	N
LIST_S2	Benign	0.75	T
M_CAP	Benign	0.0082	T
MetaRNN	Benign	0.35	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.98	N
PhyloP100		0.69
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.11
Sift	Uncertain	0.021	D
Sift4G	Benign	0.31	T
Polyphen		0.84	P
Vest4		0.20
MutPred		0.56		Gain of MoRF binding (P = 0.0056)
MVP		0.22
MPC		0.69
ClinPred		0.48	T
GERP RS		3.9
Varity_R		0.26
gMVP		0.55
Mutation Taster		=79/21	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: rs780417589; hg19: chr19-46522639;