1-156243466-G-C

Variant names:

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

Variant summary

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

The ENST00000340183.10(PAQR6):​n.*1040C>G variant causes a non coding transcript exon 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PAQR6 ENST00000340183.10 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• 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: 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 (BayesDel_noAF=-0.9).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000340183.10. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PAQR6	NM_198406.3	MANE Select	c.*663C>G		3_prime_UTR	Exon 8 of 8	NP_940798.1
	PAQR6	NR_073610.2		n.1747C>G		non_coding_transcript_exon	Exon 7 of 7
	PAQR6	NM_024897.4		c.*395C>G		3_prime_UTR	Exon 7 of 7	NP_079173.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PAQR6	ENST00000340183.10	TSL:1	n.*1040C>G		non_coding_transcript_exon	Exon 7 of 7	ENSP00000341926.6
	PAQR6	ENST00000468632.5	TSL:1	n.1980C>G		non_coding_transcript_exon	Exon 7 of 7
	PAQR6	ENST00000492619.5	TSL:1	n.1978C>G		non_coding_transcript_exon	Exon 7 of 7

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 308944 Hom.: 0 Cov.: 5 AF XY: 0.00 AC XY: 0 AN XY: 158630

African (AFR) AF: 0.00 AC: 0 AN: 10284

American (AMR) AF: 0.00 AC: 0 AN: 13132

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 9584

East Asian (EAS) AF: 0.00 AC: 0 AN: 21764

South Asian (SAS) AF: 0.00 AC: 0 AN: 22884

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 17642

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1374

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 193826

Other (OTH) AF: 0.00 AC: 0 AN: 18454

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.36
DANN	Benign	0.33
PhyloP100		-0.38

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;