rs12593391

Positions:

• chr15-69299928-T-C

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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/exons	MANE	UniProt
PAQR5	NM_017705.4	c.-277+872T>C		intron_variant		ENST00000395407.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PAQR5	ENST00000395407.7	c.-277+872T>C		intron_variant		1	NM_017705.4	P1
PAQR5	ENST00000558684.5	c.-243+872T>C		intron_variant		5

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

Gnomad4 AFR AF: 0.205

Gnomad4 AMR AF: 0.572

Gnomad4 ASJ AF: 0.608

Gnomad4 EAS AF: 0.397

Gnomad4 SAS AF: 0.529

Gnomad4 FIN AF: 0.542

Gnomad4 NFE AF: 0.614

Gnomad4 OTH AF: 0.519

Alfa AF: 0.550 Hom.: 3328

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

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

LitVar

Other links and lift over

dbSNP: rs12593391; hg19: chr15-69592267;