3-142963131-G-T

Variant names:

• chr3-142963131-G-T
• rs751225224
• NM_198504.4:c.206C>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_198504.4(PAQR9):​c.206C>A​(p.Thr69Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/22 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. T69M) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: PAQR9 NM_198504.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.53
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.33785635).

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.206C>A	p.Thr69Lys	missense	Exon 1 of 1	NP_940906.1	Q6ZVX9
	PAQR9	NM_001375300.1		c.206C>A	p.Thr69Lys	missense	Exon 2 of 4	NP_001362229.1
	PAQR9	NM_001375301.1		c.206C>A	p.Thr69Lys	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.206C>A	p.Thr69Lys	missense	Exon 1 of 1	ENSP00000341564.4	Q6ZVX9
	PAQR9	ENST00000900185.1		c.206C>A	p.Thr69Lys	missense	Exon 2 of 2	ENSP00000570244.1
	PAQR9	ENST00000900186.1		c.206C>A	p.Thr69Lys	missense	Exon 2 of 2	ENSP00000570245.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.63
BayesDel_addAF	Benign	-0.079	T
BayesDel_noAF	Benign	-0.35
CADD	Uncertain	25
DANN	Benign	0.96
DEOGEN2	Benign	0.13	T
Eigen	Benign	0.17
Eigen_PC	Benign	0.21
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.57	T
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.34	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.34	N
PhyloP100		3.5
PrimateAI	Uncertain	0.60	T
PROVEAN	Benign	-2.0	N
REVEL	Benign	0.13
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.010	D
Polyphen		0.77	P
Vest4		0.47
MutPred		0.66		Gain of methylation at T69 (P = 0.0016)
MVP		0.10
MPC		1.5
ClinPred		0.69	D
GERP RS		3.5
Varity_R		0.27
gMVP		0.90
Mutation Taster		=71/29	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: rs751225224; hg19: chr3-142681973;