15-69403910-T-C

Variant names:

• chr15-69403910-T-C
• rs1394415
• NM_017705.4:c.*88T>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.*88T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.936 in 1,396,354 control chromosomes in the GnomAD database, including 618,142 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 0.84 (56167 hom., cov: 32)
  • Exomes 𝑓: 0.95 (561975 hom.)
• Consequence: PAQR5 NM_017705.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.219
• Publications: 9 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]

KIF23-AS1 (HGNC:27075): (KIF23 and PAQR5 antisense RNA 1)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.965 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PAQR5	NM_017705.4	c.*88T>C		3_prime_UTR_variant	Exon 9 of 9	ENST00000395407.7	NP_060175.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PAQR5	ENST00000395407.7	c.*88T>C		3_prime_UTR_variant	Exon 9 of 9	1	NM_017705.4	ENSP00000378803.2

Frequencies

GnomAD3 genomes AF: 0.845 AC: 128400 AN: 152024 Hom.: 56156 Cov.: 32

Gnomad AFR AF: 0.612

Gnomad AMI AF: 0.976

Gnomad AMR AF: 0.826

Gnomad ASJ AF: 0.964

Gnomad EAS AF: 0.705

Gnomad SAS AF: 0.950

Gnomad FIN AF: 0.923

Gnomad MID AF: 0.921

Gnomad NFE AF: 0.972

Gnomad OTH AF: 0.875

GnomAD4 exome AF: 0.947 AC: 1178490 AN: 1244210 Hom.: 561975 Cov.: 17 AF XY: 0.949 AC XY: 588211 AN XY: 619698

African (AFR) AF: 0.617 AC: 17263 AN: 27988

American (AMR) AF: 0.754 AC: 25582 AN: 33932

Ashkenazi Jewish (ASJ) AF: 0.971 AC: 20408 AN: 21018

East Asian (EAS) AF: 0.705 AC: 27038 AN: 38372

South Asian (SAS) AF: 0.958 AC: 67233 AN: 70162

European-Finnish (FIN) AF: 0.933 AC: 36008 AN: 38588

Middle Eastern (MID) AF: 0.943 AC: 4715 AN: 4998

European-Non Finnish (NFE) AF: 0.974 AC: 931143 AN: 956298

Other (OTH) AF: 0.929 AC: 49100 AN: 52854

GnomAD4 genome AF: 0.844 AC: 128447 AN: 152144 Hom.: 56167 Cov.: 32 AF XY: 0.842 AC XY: 62625 AN XY: 74372

African (AFR) AF: 0.612 AC: 25357 AN: 41438

American (AMR) AF: 0.826 AC: 12628 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.964 AC: 3346 AN: 3472

East Asian (EAS) AF: 0.705 AC: 3647 AN: 5172

South Asian (SAS) AF: 0.949 AC: 4577 AN: 4824

European-Finnish (FIN) AF: 0.923 AC: 9792 AN: 10606

Middle Eastern (MID) AF: 0.922 AC: 271 AN: 294

European-Non Finnish (NFE) AF: 0.972 AC: 66091 AN: 68026

Other (OTH) AF: 0.876 AC: 1848 AN: 2110

Alfa AF: 0.935 Hom.: 273502

Bravo AF: 0.824

Asia WGS AF: 0.810 AC: 2817 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	3.3
DANN	Benign	0.57
PhyloP100		0.22
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1394415; hg19: chr15-69696249; COSMIC: COSV61818254; COSMIC: COSV61818254;