chr15-69403973-G-A

Variant names:

• chr15-69403973-G-A
• rs3743096
• NM_017705.4:c.*151G>A

Variant summary

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

The NM_017705.4(PAQR5):​c.*151G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000015 in 667,058 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 33)
  • Exomes 𝑓: 0.0000015 (0 hom.)
• Consequence: PAQR5 NM_017705.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.375
• Publications: 5 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: 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=-0.87).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017705.4. 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
	PAQR5	NM_017705.4	MANE Select	c.*151G>A		3_prime_UTR	Exon 9 of 9	NP_060175.3
	KIF23-AS1	NR_132969.1		n.1186C>T		non_coding_transcript_exon	Exon 2 of 2
	PAQR5	NM_001104554.2		c.*151G>A		3_prime_UTR	Exon 9 of 9	NP_001098024.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PAQR5	ENST00000395407.7	TSL:1 MANE Select	c.*151G>A		3_prime_UTR	Exon 9 of 9	ENSP00000378803.2
	PAQR5	ENST00000340965.4	TSL:1	c.*151G>A		3_prime_UTR	Exon 7 of 7	ENSP00000343877.3
	KIF23-AS1	ENST00000558107.2	TSL:3	n.380C>T		non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000150 AC: 1 AN: 667058 Hom.: 0 Cov.: 9 AF XY: 0.00 AC XY: 0 AN XY: 343484

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 16388

American (AMR) AF: 0.00 AC: 0 AN: 20606

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15236

East Asian (EAS) AF: 0.00 AC: 0 AN: 32884

South Asian (SAS) AF: 0.00 AC: 0 AN: 49464

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 31348

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2442

European-Non Finnish (NFE) AF: 0.00000215 AC: 1 AN: 465312

Other (OTH) AF: 0.00 AC: 0 AN: 33378

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 1144

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.2
DANN	Benign	0.24
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: rs3743096; hg19: chr15-69696312;