NM_152341.5:c.440C>T

Variant names:

• chr16-2971566-C-T
• rs768657479
• NM_152341.5:c.440C>T

Variant summary

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

The NM_152341.5(PAQR4):​c.440C>T​(p.Pro147Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000219 in 1,597,330 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. P147P) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.000039 (0 hom., cov: 34)
  • Exomes 𝑓: 0.000020 (0 hom.)
• Consequence: PAQR4 NM_152341.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.15
• Publications: 0 publications found

Genes affected

PAQR4 (HGNC:26386): (progestin and adipoQ receptor family member 4) Predicted to enable signaling receptor activity. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

PKMYT1 (HGNC:29650): (protein kinase, membrane associated tyrosine/threonine 1) This gene encodes a member of the serine/threonine protein kinase family. The encoded protein is a membrane-associated kinase that negatively regulates the G2/M transition of the cell cycle by phosphorylating and inactivating cyclin-dependent kinase 1. The activity of the encoded protein is regulated by polo-like kinase 1. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, May 2012]

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=0.09545344).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152341.5. 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
	PAQR4	NM_152341.5	MANE Select	c.440C>T	p.Pro147Leu	missense	Exon 3 of 3	NP_689554.2
	PAQR4	NM_001284511.2		c.323C>T	p.Pro108Leu	missense	Exon 3 of 3	NP_001271440.1	Q8N4S7-2
	PAQR4	NM_001284513.2		c.239C>T	p.Pro80Leu	missense	Exon 3 of 3	NP_001271442.1	I3L1A2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PAQR4	ENST00000318782.9	TSL:1 MANE Select	c.440C>T	p.Pro147Leu	missense	Exon 3 of 3	ENSP00000321804.8	Q8N4S7-1
	PAQR4	ENST00000293978.12	TSL:2	c.323C>T	p.Pro108Leu	missense	Exon 3 of 3	ENSP00000293978.8	Q8N4S7-2
	PAQR4	ENST00000896898.1		c.287C>T	p.Pro96Leu	missense	Exon 3 of 3	ENSP00000566957.1

Frequencies

GnomAD3 genomes AF: 0.0000394 AC: 6 AN: 152238 Hom.: 0 Cov.: 34

Gnomad AFR AF: 0.000121

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: 0.0000127 AC: 3 AN: 236466 AF XY: 0.0000154

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000291

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000551

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000912

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000201 AC: 29 AN: 1444974 Hom.: 0 Cov.: 32 AF XY: 0.0000209 AC XY: 15 AN XY: 718740

African (AFR) AF: 0.0000299 AC: 1 AN: 33416

American (AMR) AF: 0.00 AC: 0 AN: 44578

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26036

East Asian (EAS) AF: 0.0000505 AC: 2 AN: 39592

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86094

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 39774

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5752

European-Non Finnish (NFE) AF: 0.0000216 AC: 24 AN: 1109600

Other (OTH) AF: 0.0000166 AC: 1 AN: 60132

GnomAD4 genome AF: 0.0000394 AC: 6 AN: 152356 Hom.: 0 Cov.: 34 AF XY: 0.0000671 AC XY: 5 AN XY: 74498

African (AFR) AF: 0.000120 AC: 5 AN: 41586

American (AMR) AF: 0.00 AC: 0 AN: 15310

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: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68030

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

Alfa AF: 0.0000616 Hom.: 0

Bravo AF: 0.0000340

ExAC AF: 0.00000827 AC: 1

EpiCase AF: 0.0000545

EpiControl AF: 0.00

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	0.12
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	21
DANN	Benign	0.90
DEOGEN2	Benign	0.0076	T
Eigen	Benign	-0.69
Eigen_PC	Benign	-0.45
FATHMM_MKL	Benign	0.71	D
LIST_S2	Benign	0.75	T
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.095	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-1.2	N
PhyloP100		2.1
PrimateAI	Uncertain	0.66	T
PROVEAN	Benign	-0.15	N
REVEL	Benign	0.13
Sift	Benign	0.65	T
Sift4G	Benign	0.37	T
Polyphen		0.0010	B
Vest4		0.30
MutPred		0.48		Loss of catalytic residue at P147 (P = 0.0119)
MVP		0.10
MPC		0.15
ClinPred		0.12	T
GERP RS		5.0
Varity_R		0.11
gMVP		0.49
Mutation Taster		=69/31	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: rs768657479; hg19: chr16-3021567; COSMIC: COSV51891597; COSMIC: COSV51891597;