NM_017705.4:c.592C>T

Variant names:

• chr15-69397547-C-T
• rs542373751
• NM_017705.4:c.592C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_017705.4(PAQR5):​c.592C>T​(p.Leu198Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000995 in 1,608,302 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000010 (0 hom.)
• Consequence: PAQR5 NM_017705.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.64
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.13089854).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PAQR5	NM_017705.4	MANE Select	c.592C>T	p.Leu198Phe	missense	Exon 7 of 9	NP_060175.3
	PAQR5	NM_001104554.2		c.592C>T	p.Leu198Phe	missense	Exon 7 of 9	NP_001098024.1	Q9NXK6
	KIF23-AS1	NR_132970.1		n.1135G>A		non_coding_transcript_exon	Exon 3 of 3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PAQR5	ENST00000395407.7	TSL:1 MANE Select	c.592C>T	p.Leu198Phe	missense	Exon 7 of 9	ENSP00000378803.2	Q9NXK6
	PAQR5	ENST00000340965.4	TSL:1	c.592C>T	p.Leu198Phe	missense	Exon 5 of 7	ENSP00000343877.3	Q9NXK6
	PAQR5	ENST00000561153.5	TSL:5	c.592C>T	p.Leu198Phe	missense	Exon 7 of 9	ENSP00000453526.1	Q9NXK6

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152224 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000119 AC: 3 AN: 251486 AF XY: 0.0000147

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000103 AC: 15 AN: 1455960 Hom.: 0 Cov.: 28 AF XY: 0.0000124 AC XY: 9 AN XY: 724772

African (AFR) AF: 0.00 AC: 0 AN: 33370

American (AMR) AF: 0.00 AC: 0 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26100

East Asian (EAS) AF: 0.000176 AC: 7 AN: 39662

South Asian (SAS) AF: 0.0000580 AC: 5 AN: 86134

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53416

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5758

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1106582

Other (OTH) AF: 0.0000498 AC: 3 AN: 60222

GnomAD4 genome AF: 0.00000656 AC: 1 AN: 152342 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74490

African (AFR) AF: 0.00 AC: 0 AN: 41582

American (AMR) AF: 0.00 AC: 0 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68036

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Benign	0.049	T
Eigen	Benign	-0.50
Eigen_PC	Benign	-0.46
FATHMM_MKL	Benign	0.60	D
LIST_S2	Benign	0.82	T
M_CAP	Benign	0.0053	T
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-1.1	T
PhyloP100		1.6
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-1.7	N
REVEL	Benign	0.042
Sift	Benign	0.092	T
Sift4G	Benign	0.19	T
Polyphen		0.0020	B
Vest4		0.16
MutPred		0.59		Loss of helix (P = 0.0558)
MVP		0.22
MPC		0.22
ClinPred		0.20	T
GERP RS		-0.51
Varity_R		0.049
gMVP		0.39
Mutation Taster		=74/26	polymorphism

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: rs542373751; hg19: chr15-69689886;