chr3-142963312-C-T

Variant names:

• chr3-142963312-C-T
• rs1934949530
• NM_198504.4:c.25G>A

Variant summary

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

The NM_198504.4(PAQR9):​c.25G>A​(p.Gly9Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000661 in 151,396 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G9D) has been classified as Uncertain significance.

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
• Consequence: PAQR9 NM_198504.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.116
• Publications: 0 publications found

Genes affected

PAQR9 (HGNC:30131): (progestin and adipoQ receptor family member 9) Predicted to enable signaling receptor activity. Predicted to be located in plasma membrane. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

PAQR9-AS1 (HGNC:50861): (PAQR9 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 (MetaRNN=0.043291688).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_198504.4. 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
	PAQR9	NM_198504.4	MANE Select	c.25G>A	p.Gly9Ser	missense	Exon 1 of 1	NP_940906.1	Q6ZVX9
	PAQR9	NM_001375300.1		c.25G>A	p.Gly9Ser	missense	Exon 2 of 4	NP_001362229.1
	PAQR9	NM_001375301.1		c.25G>A	p.Gly9Ser	missense	Exon 2 of 4	NP_001362230.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PAQR9	ENST00000340634.6	TSL:6 MANE Select	c.25G>A	p.Gly9Ser	missense	Exon 1 of 1	ENSP00000341564.4	Q6ZVX9
	PAQR9	ENST00000900185.1		c.25G>A	p.Gly9Ser	missense	Exon 2 of 2	ENSP00000570244.1
	PAQR9	ENST00000900186.1		c.25G>A	p.Gly9Ser	missense	Exon 2 of 2	ENSP00000570245.1

Frequencies

GnomAD3 genomes AF: 0.00000661 AC: 1 AN: 151288 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000242

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: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 30

GnomAD4 genome AF: 0.00000661 AC: 1 AN: 151396 Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1 AN XY: 74010

African (AFR) AF: 0.0000241 AC: 1 AN: 41422

American (AMR) AF: 0.00 AC: 0 AN: 15228

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3462

East Asian (EAS) AF: 0.00 AC: 0 AN: 5098

South Asian (SAS) AF: 0.00 AC: 0 AN: 4818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10298

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 290

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67762

Other (OTH) AF: 0.00 AC: 0 AN: 2106

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	-0.35	T
BayesDel_noAF	Benign	-0.75
CADD	Benign	17
DANN	Benign	0.97
DEOGEN2	Benign	0.012	T
Eigen	Benign	-0.82
Eigen_PC	Benign	-0.74
FATHMM_MKL	Benign	0.22	N
LIST_S2	Benign	0.52	T
M_CAP	Benign	0.059	D
MetaRNN	Benign	0.043	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.55	N
PhyloP100		0.12
PrimateAI	Pathogenic	0.87	D
PROVEAN	Benign	-0.20	N
REVEL	Benign	0.034
Sift	Benign	0.25	T
Sift4G	Benign	0.28	T
Polyphen		0.0	B
Vest4		0.077
MutPred		0.16		Loss of glycosylation at K13 (P = 0.0192)
MVP		0.082
MPC		1.1
ClinPred		0.22	T
GERP RS		0.87
PromoterAI		0.00060	Neutral
Varity_R		0.092
gMVP		0.32
Mutation Taster		=99/1	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: rs1934949530; hg19: chr3-142682154;