11-57380702-A-T

Variant names:

• chr11-57380702-A-T
• rs669661
• NM_006093.4:c.7T>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_006093.4(PRG3):​c.7T>A​(p.Cys3Ser) 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. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000029 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PRG3 NM_006093.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.884
• Publications: 22 publications found

Genes affected

PRG3 (HGNC:9363): (proteoglycan 3, pro eosinophil major basic protein 2) An extracellular matrix structural constituent conferring compression resistance. Involved in several processes, including granulocyte activation; histamine biosynthetic process; and regulation of gene expression. Located in collagen-containing extracellular matrix. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.045143217).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRG3	NM_006093.4	c.7T>A	p.Cys3Ser	missense_variant	Exon 2 of 6	ENST00000287143.2	NP_006084.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRG3	ENST00000287143.2	c.7T>A	p.Cys3Ser	missense_variant	Exon 2 of 6	1	NM_006093.4	ENSP00000287143.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000285 AC: 4 AN: 1403176 Hom.: 0 Cov.: 41 AF XY: 0.00000144 AC XY: 1 AN XY: 696458

African (AFR) AF: 0.00 AC: 0 AN: 30054

American (AMR) AF: 0.00 AC: 0 AN: 31914

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24404

East Asian (EAS) AF: 0.00 AC: 0 AN: 36338

South Asian (SAS) AF: 0.00 AC: 0 AN: 76032

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52336

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5630

European-Non Finnish (NFE) AF: 0.00000367 AC: 4 AN: 1088474

Other (OTH) AF: 0.00 AC: 0 AN: 57994

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.092
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.79
CADD	Benign	0.59
DANN	Benign	0.52
DEOGEN2	Benign	0.0098	T
Eigen	Benign	-1.8
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.035	N
LIST_S2	Benign	0.17	T
M_CAP	Benign	0.0033	T
MetaRNN	Benign	0.045	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	1.4	L
PhyloP100		-0.88
PrimateAI	Benign	0.20	T
PROVEAN	Benign	0.24	N
REVEL	Benign	0.014
Sift	Benign	0.37	T
Sift4G	Benign	0.88	T
Polyphen		0.0	B
Vest4		0.063
MutPred		0.35		Loss of catalytic residue at M1 (P = 4e-04);
MVP		0.13
MPC		0.20
ClinPred		0.092	T
GERP RS		-6.0
PromoterAI		-0.011	Neutral
Varity_R		0.040
gMVP		0.35
Mutation Taster		=100/0	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: rs669661; hg19: chr11-57148175;