dbSNP rs587779753: PAQR6:n.*1040C>G (chr1-156243466-G-C) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.382

Publications

27 publications found

Variant links:

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]

PAQR6 links:

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]

BGLAP links:

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]

PMF1-BGLAP links:

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ACMG classification

Classification was made for transcript

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).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PAQR6	NM_198406.3 link	c.*663C>G		3_prime_UTR_variant	Exon 8 of 8	ENST00000292291.10	NP_940798.1	Q6TCH4-1Q5TCK7
BGLAP	NM_199173.6 link	c.*304G>C		downstream_gene_variant		ENST00000368272.5	NP_954642.1	P02818

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
PAQR6	ENST00000292291.10 link	c.*663C>G	3_prime_UTR_variant	Exon 8 of 8	1	NM_198406.3	ENSP00000292291.5	Q6TCH4-1
BGLAP	ENST00000368272.5 link	c.*304G>C	downstream_gene_variant		1	NM_199173.6	ENSP00000357255.4	P02818
PMF1-BGLAP	ENST00000490491.5 link	c.*471G>C	downstream_gene_variant		2		ENSP00000475561.1	U3KQ54

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

308944

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

158630

African (AFR)

AF:

0.00

AC:

AN:

10284

American (AMR)

AF:

0.00

AC:

AN:

13132

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

9584

East Asian (EAS)

AF:

0.00

AC:

AN:

21764

South Asian (SAS)

AF:

0.00

AC:

AN:

22884

European-Finnish (FIN)

AF:

0.00

AC:

AN:

17642

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1374

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

193826

Other (OTH)

AF:

0.00

AC:

AN:

18454

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.36

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over