rs759330

Variant names:

• chr1-156243466-G-A
• rs759330
• ENST00000340183.10:n.*1040C>T

Your query was ambiguous. Multiple possible variants found:

• chr1-156243466-G-A
• chr1-156243466-G-C

Variant summary

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

The ENST00000340183.10(PAQR6):​n.*1040C>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.737 in 460,080 control chromosomes in the GnomAD database, including 126,266 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as association (no stars).

• Frequency:
  • Genomes: 𝑓 0.75 (42878 hom., cov: 31)
  • Exomes 𝑓: 0.73 (83388 hom.)
• Consequence: PAQR6 ENST00000340183.10 non_coding_transcript_exon
• Clinical Significance: association no assertion criteria provided O:1
• Conservation: PhyloP100: -0.382
• Publications: 27 publications found

Genes affected

PAQR6 (HGNC:30132): (progestin and adipoQ receptor family member 6) Predicted to enable signaling receptor activity. Predicted to be located in plasma membrane. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

BGLAP (HGNC:1043): (bone gamma-carboxyglutamate protein) This gene encodes a highly abundant bone protein secreted by osteoblasts that regulates bone remodeling and energy metabolism. The encoded protein contains a Gla (gamma carboxyglutamate) domain, which functions in binding to calcium and hydroxyapatite, the mineral component of bone. Serum osteocalcin levels may be negatively correlated with metabolic syndrome. Read-through transcription exists between this gene and the neighboring upstream gene, PMF1 (polyamine-modulated factor 1), but the encoded protein only shows sequence identity with the upstream gene product. [provided by RefSeq, Jun 2015]

PMF1-BGLAP (HGNC:42953): (PMF1-BGLAP readthrough) This locus represents naturally occurring read-through transcription between the neighboring PMF1 (polyamine-modulated factor 1) and BGLAP (bone gamma-carboxyglutamate Gla protein) genes on chromosome 1. Alternative splicing results in multiple transcript variants encoding isoforms that share sequence identity with the upstream gene product, but they contain distinct C-termini due to frameshifts versus the downstream gene coding sequence. [provided by RefSeq, Dec 2010]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.802 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PAQR6	NM_198406.3	c.*663C>T		3_prime_UTR_variant	Exon 8 of 8	ENST00000292291.10	NP_940798.1
BGLAP	NM_199173.6	c.*304G>A		downstream_gene_variant		ENST00000368272.5	NP_954642.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PAQR6	ENST00000292291.10	c.*663C>T		3_prime_UTR_variant	Exon 8 of 8	1	NM_198406.3	ENSP00000292291.5
BGLAP	ENST00000368272.5	c.*304G>A		downstream_gene_variant		1	NM_199173.6	ENSP00000357255.4
PMF1-BGLAP	ENST00000490491.5	c.*471G>A		downstream_gene_variant		2		ENSP00000475561.1

Frequencies

GnomAD3 genomes AF: 0.748 AC: 113606 AN: 151846 Hom.: 42825 Cov.: 31

Gnomad AFR AF: 0.801

Gnomad AMI AF: 0.764

Gnomad AMR AF: 0.814

Gnomad ASJ AF: 0.792

Gnomad EAS AF: 0.762

Gnomad SAS AF: 0.789

Gnomad FIN AF: 0.547

Gnomad MID AF: 0.715

Gnomad NFE AF: 0.726

Gnomad OTH AF: 0.753

GnomAD4 exome AF: 0.732 AC: 225525 AN: 308116 Hom.: 83388 Cov.: 5 AF XY: 0.734 AC XY: 116160 AN XY: 158180

African (AFR) AF: 0.803 AC: 8250 AN: 10270

American (AMR) AF: 0.841 AC: 11031 AN: 13118

Ashkenazi Jewish (ASJ) AF: 0.785 AC: 7508 AN: 9564

East Asian (EAS) AF: 0.736 AC: 15976 AN: 21696

South Asian (SAS) AF: 0.777 AC: 17735 AN: 22814

European-Finnish (FIN) AF: 0.567 AC: 9983 AN: 17604

Middle Eastern (MID) AF: 0.749 AC: 1028 AN: 1372

European-Non Finnish (NFE) AF: 0.727 AC: 140486 AN: 193286

Other (OTH) AF: 0.736 AC: 13528 AN: 18392

GnomAD4 genome AF: 0.748 AC: 113719 AN: 151964 Hom.: 42878 Cov.: 31 AF XY: 0.743 AC XY: 55200 AN XY: 74250

African (AFR) AF: 0.802 AC: 33218 AN: 41442

American (AMR) AF: 0.814 AC: 12434 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.792 AC: 2748 AN: 3470

East Asian (EAS) AF: 0.761 AC: 3938 AN: 5174

South Asian (SAS) AF: 0.789 AC: 3794 AN: 4808

European-Finnish (FIN) AF: 0.547 AC: 5756 AN: 10522

Middle Eastern (MID) AF: 0.724 AC: 213 AN: 294

European-Non Finnish (NFE) AF: 0.726 AC: 49333 AN: 67970

Other (OTH) AF: 0.755 AC: 1591 AN: 2106

Alfa AF: 0.748 Hom.: 56249

Bravo AF: 0.771

Asia WGS AF: 0.799 AC: 2779 AN: 3478

ClinVar

Significance: association

Submissions summary: Other:1

Revision: no assertion criteria provided

Submissions by phenotype

Nephrolithiasis, calcium oxalate Other:1

Mar 01, 2014

Division of Molecular Genetics and Division of Molecular Medicine, Department of Research and Development, Faculty of Medicine Siriraj Hospital, Mahidol University

Significance: association

Review Status: no assertion criteria provided

Collection Method: case-control

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.58
DANN	Benign	0.30
PhyloP100		-0.38
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: rs759330; hg19: chr1-156213257;