NM_152341.5:c.441G>A

Variant names:

• chr16-2971567-G-A
• rs776685080
• NM_152341.5:c.441G>A

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4_Strong BP6_Moderate BP7

The NM_152341.5(PAQR4):​c.441G>A​(p.Pro147Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000689 in 1,597,380 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000085 (0 hom., cov: 34)
  • Exomes 𝑓: 0.000067 (0 hom.)
• Consequence: PAQR4 NM_152341.5 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -4.47
• Publications: 1 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: Benign. The variant received -7 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.7).
• BP6: Variant 16-2971567-G-A is Benign according to our data. Variant chr16-2971567-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 3885594.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-4.47 with no splicing effect.

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.441G>A	p.Pro147Pro	synonymous	Exon 3 of 3	NP_689554.2
	PAQR4	NM_001284511.2		c.324G>A	p.Pro108Pro	synonymous	Exon 3 of 3	NP_001271440.1	Q8N4S7-2
	PAQR4	NM_001284513.2		c.240G>A	p.Pro80Pro	synonymous	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.441G>A	p.Pro147Pro	synonymous	Exon 3 of 3	ENSP00000321804.8	Q8N4S7-1
	PAQR4	ENST00000293978.12	TSL:2	c.324G>A	p.Pro108Pro	synonymous	Exon 3 of 3	ENSP00000293978.8	Q8N4S7-2
	PAQR4	ENST00000896898.1		c.288G>A	p.Pro96Pro	synonymous	Exon 3 of 3	ENSP00000566957.1

Frequencies

GnomAD3 genomes AF: 0.0000854 AC: 13 AN: 152206 Hom.: 0 Cov.: 34

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000191

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000381 AC: 9 AN: 236522 AF XY: 0.0000463

Gnomad AFR exome AF: 0.0000664

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000551

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000547

Gnomad OTH exome AF: 0.000168

GnomAD4 exome AF: 0.0000671 AC: 97 AN: 1445174 Hom.: 0 Cov.: 32 AF XY: 0.0000765 AC XY: 55 AN XY: 718872

African (AFR) AF: 0.0000599 AC: 2 AN: 33406

American (AMR) AF: 0.00 AC: 0 AN: 44580

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26054

East Asian (EAS) AF: 0.0000253 AC: 1 AN: 39584

South Asian (SAS) AF: 0.0000697 AC: 6 AN: 86122

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 39890

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5754

European-Non Finnish (NFE) AF: 0.0000712 AC: 79 AN: 1109662

Other (OTH) AF: 0.000150 AC: 9 AN: 60122

GnomAD4 genome AF: 0.0000854 AC: 13 AN: 152206 Hom.: 0 Cov.: 34 AF XY: 0.0000269 AC XY: 2 AN XY: 74364

African (AFR) AF: 0.00 AC: 0 AN: 41450

American (AMR) AF: 0.00 AC: 0 AN: 15288

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5196

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: 316

European-Non Finnish (NFE) AF: 0.000191 AC: 13 AN: 68024

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.000214 Hom.: 0

Bravo AF: 0.0000680

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	1.1
DANN	Benign	0.85
PhyloP100		-4.5

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: rs776685080; hg19: chr16-3021568; COSMIC: COSV51890758; COSMIC: COSV51890758;