3-142963228-G-C

Variant names:

• chr3-142963228-G-C
• rs766969033
• NM_198504.4:c.109C>G

Variant summary

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

The NM_198504.4(PAQR9):​c.109C>G​(p.Pro37Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000715 in 1,398,674 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P37S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: PAQR9 NM_198504.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.379
• 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: 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=0.07286692).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PAQR9	NM_198504.4	c.109C>G	p.Pro37Ala	missense_variant	Exon 1 of 1	ENST00000340634.6	NP_940906.1
PAQR9	NM_001375300.1	c.109C>G	p.Pro37Ala	missense_variant	Exon 2 of 4		NP_001362229.1
PAQR9	NM_001375301.1	c.109C>G	p.Pro37Ala	missense_variant	Exon 2 of 4		NP_001362230.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PAQR9	ENST00000340634.6	c.109C>G	p.Pro37Ala	missense_variant	Exon 1 of 1	6	NM_198504.4	ENSP00000341564.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.15e-7 AC: 1 AN: 1398674 Hom.: 0 Cov.: 31 AF XY: 0.00000145 AC XY: 1 AN XY: 689840

African (AFR) AF: 0.00 AC: 0 AN: 31792

American (AMR) AF: 0.00 AC: 0 AN: 36270

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25192

East Asian (EAS) AF: 0.00 AC: 0 AN: 35886

South Asian (SAS) AF: 0.0000125 AC: 1 AN: 79854

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 45886

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5666

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1080196

Other (OTH) AF: 0.00 AC: 0 AN: 57932

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.051
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	11
DANN	Benign	0.84
DEOGEN2	Benign	0.011	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.051	N
LIST_S2	Benign	0.40	T
M_CAP	Benign	0.0055	T
MetaRNN	Benign	0.073	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.34	N
PhyloP100		-0.38
PrimateAI	Uncertain	0.68	T
PROVEAN	Benign	0.30	N
REVEL	Benign	0.0070
Sift	Benign	0.093	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.11
MutPred		0.29		Loss of glycosylation at P37 (P = 0.0035);
MVP		0.068
MPC		1.1
ClinPred		0.076	T
GERP RS		-1.4
PromoterAI		0.012	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.020
gMVP		0.44
Mutation Taster		=100/0	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: rs766969033; hg19: chr3-142682070;