11-57380702-A-G

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006093.4(PRG3):​c.7T>C​(p.Cys3Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.993 in 1,555,408 control chromosomes in the GnomAD database, including 766,868 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 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: 𝑓 0.96 (70708 hom., cov: 32)
  • Exomes 𝑓: 1.0 (696160 hom.)
• 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=1.5357821E-6).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.993 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRG3	NM_006093.4	c.7T>C	p.Cys3Arg	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>C	p.Cys3Arg	missense_variant	Exon 2 of 6	1	NM_006093.4	ENSP00000287143.2

Frequencies

GnomAD3 genomes AF: 0.962 AC: 146326 AN: 152154 Hom.: 70671 Cov.: 32

Gnomad AFR AF: 0.868

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.987

Gnomad ASJ AF: 1.00

Gnomad EAS AF: 0.998

Gnomad SAS AF: 0.994

Gnomad FIN AF: 1.00

Gnomad MID AF: 0.991

Gnomad NFE AF: 0.999

Gnomad OTH AF: 0.971

GnomAD2 exomes AF: 0.989 AC: 189461 AN: 191506 AF XY: 0.992

Gnomad AFR exome AF: 0.859

Gnomad AMR exome AF: 0.993

Gnomad ASJ exome AF: 1.00

Gnomad EAS exome AF: 0.999

Gnomad FIN exome AF: 1.00

Gnomad NFE exome AF: 1.00

Gnomad OTH exome AF: 0.995

GnomAD4 exome AF: 0.996 AC: 1397371 AN: 1403136 Hom.: 696160 Cov.: 41 AF XY: 0.996 AC XY: 693886 AN XY: 696440

African (AFR) AF: 0.856 AC: 25710 AN: 30020

American (AMR) AF: 0.992 AC: 31666 AN: 31912

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 24403 AN: 24404

East Asian (EAS) AF: 0.999 AC: 36316 AN: 36338

South Asian (SAS) AF: 0.996 AC: 75705 AN: 76028

European-Finnish (FIN) AF: 1.00 AC: 52327 AN: 52336

Middle Eastern (MID) AF: 0.994 AC: 5598 AN: 5630

European-Non Finnish (NFE) AF: 1.00 AC: 1088198 AN: 1088476

Other (OTH) AF: 0.991 AC: 57448 AN: 57992

GnomAD4 genome AF: 0.962 AC: 146420 AN: 152272 Hom.: 70708 Cov.: 32 AF XY: 0.964 AC XY: 71739 AN XY: 74454

African (AFR) AF: 0.867 AC: 36023 AN: 41526

American (AMR) AF: 0.987 AC: 15105 AN: 15306

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 3472 AN: 3472

East Asian (EAS) AF: 0.998 AC: 5155 AN: 5166

South Asian (SAS) AF: 0.994 AC: 4798 AN: 4828

European-Finnish (FIN) AF: 1.00 AC: 10615 AN: 10618

Middle Eastern (MID) AF: 0.993 AC: 292 AN: 294

European-Non Finnish (NFE) AF: 0.999 AC: 67997 AN: 68038

Other (OTH) AF: 0.971 AC: 2051 AN: 2112

Alfa AF: 0.991 Hom.: 156958

Bravo AF: 0.956

TwinsUK AF: 1.00 AC: 3707

ALSPAC AF: 1.00 AC: 3854

ESP6500AA AF: 0.867 AC: 3815

ESP6500EA AF: 0.999 AC: 8583

ExAC AF: 0.986 AC: 119344

Asia WGS AF: 0.984 AC: 3423 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.082
BayesDel_addAF	Benign	-0.84	T
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.2
DANN	Benign	0.54
DEOGEN2	Benign	0.0079	T
Eigen	Benign	-1.8
Eigen_PC	Benign	-1.9
FATHMM_MKL	Benign	0.0039	N
LIST_S2	Benign	0.15	T
MetaRNN	Benign	0.0000015	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.69	N
PhyloP100		-0.88
PrimateAI	Benign	0.21	T
PROVEAN	Benign	0.62	N
REVEL	Benign	0.014
Sift	Benign	0.88	T
Sift4G	Benign	0.70	T
Polyphen		0.0	B
Vest4		0.036
MPC		0.24
ClinPred		0.00087	T
GERP RS		-6.0
PromoterAI		0.012	Neutral
Varity_R		0.10
gMVP		0.41
Mutation Taster		=100/0	polymorphism (auto)

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; COSMIC: COSV107278984;