rs12593391

Variant names:

• chr15-69299928-T-C
• rs12593391
• NM_017705.4:c.-277+872T>C

Variant summary

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

The NM_017705.4(PAQR5):​c.-277+872T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.482 in 151,942 control chromosomes in the GnomAD database, including 20,110 homozygotes. 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: 𝑓 0.48 (20110 hom., cov: 31)
• Consequence: PAQR5 NM_017705.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.454
• Publications: 3 publications found

Genes affected

PAQR5 (HGNC:29645): (progestin and adipoQ receptor family member 5) Predicted to enable signaling receptor activity. Predicted to be involved in oogenesis. Predicted to be located in plasma membrane. Predicted to be integral component of membrane. [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 (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.609 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PAQR5	NM_017705.4	c.-277+872T>C		intron_variant	Intron 1 of 8	ENST00000395407.7	NP_060175.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PAQR5	ENST00000395407.7	c.-277+872T>C		intron_variant	Intron 1 of 8	1	NM_017705.4	ENSP00000378803.2
PAQR5	ENST00000558684.5	c.-243+872T>C		intron_variant	Intron 1 of 4	5		ENSP00000453009.1

Frequencies

GnomAD3 genomes AF: 0.482 AC: 73192 AN: 151824 Hom.: 20116 Cov.: 31

Gnomad AFR AF: 0.205

Gnomad AMI AF: 0.648

Gnomad AMR AF: 0.571

Gnomad ASJ AF: 0.608

Gnomad EAS AF: 0.397

Gnomad SAS AF: 0.530

Gnomad FIN AF: 0.542

Gnomad MID AF: 0.620

Gnomad NFE AF: 0.614

Gnomad OTH AF: 0.526

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.482 AC: 73189 AN: 151942 Hom.: 20110 Cov.: 31 AF XY: 0.480 AC XY: 35634 AN XY: 74262

African (AFR) AF: 0.205 AC: 8486 AN: 41470

American (AMR) AF: 0.572 AC: 8726 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.608 AC: 2110 AN: 3470

East Asian (EAS) AF: 0.397 AC: 2041 AN: 5140

South Asian (SAS) AF: 0.529 AC: 2549 AN: 4818

European-Finnish (FIN) AF: 0.542 AC: 5708 AN: 10538

Middle Eastern (MID) AF: 0.616 AC: 181 AN: 294

European-Non Finnish (NFE) AF: 0.614 AC: 41708 AN: 67930

Other (OTH) AF: 0.519 AC: 1093 AN: 2108

Alfa AF: 0.541 Hom.: 7247

Bravo AF: 0.472

Asia WGS AF: 0.443 AC: 1540 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.8
DANN	Benign	0.70
PhyloP100		-0.45
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: rs12593391; hg19: chr15-69592267;