rs7513351

Variant names:

• chr1-156244130-C-T
• rs7513351
• ENST00000623241.3:c.367G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000623241.3(PAQR6):​c.367G>A​(p.Glu123Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.172 in 1,603,656 control chromosomes in the GnomAD database, including 25,552 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.17 (2461 hom., cov: 33)
  • Exomes 𝑓: 0.17 (23091 hom.)
• Consequence: PAQR6 ENST00000623241.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.812
• Publications: 25 publications found

Genes affected

PAQR6 (HGNC:30132): (progestin and adipoQ receptor family member 6) 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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.004408896).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.257 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PAQR6	NM_198406.3	c.1034G>A	p.Ter345Ter	stop_retained_variant	Exon 8 of 8	ENST00000292291.10	NP_940798.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PAQR6	ENST00000292291.10	c.1034G>A	p.Ter345Ter	stop_retained_variant	Exon 8 of 8	1	NM_198406.3	ENSP00000292291.5

Frequencies

GnomAD3 genomes AF: 0.172 AC: 26220 AN: 152116 Hom.: 2444 Cov.: 33

Gnomad AFR AF: 0.157

Gnomad AMI AF: 0.128

Gnomad AMR AF: 0.263

Gnomad ASJ AF: 0.231

Gnomad EAS AF: 0.247

Gnomad SAS AF: 0.266

Gnomad FIN AF: 0.0805

Gnomad MID AF: 0.222

Gnomad NFE AF: 0.160

Gnomad OTH AF: 0.181

GnomAD2 exomes AF: 0.196 AC: 48606 AN: 247640 AF XY: 0.195

Gnomad AFR exome AF: 0.158

Gnomad AMR exome AF: 0.315

Gnomad ASJ exome AF: 0.223

Gnomad EAS exome AF: 0.243

Gnomad FIN exome AF: 0.0806

Gnomad NFE exome AF: 0.163

Gnomad OTH exome AF: 0.186

GnomAD4 exome AF: 0.171 AC: 248843 AN: 1451422 Hom.: 23091 Cov.: 32 AF XY: 0.174 AC XY: 125048 AN XY: 720144

African (AFR) AF: 0.155 AC: 5149 AN: 33298

American (AMR) AF: 0.312 AC: 13846 AN: 44394

Ashkenazi Jewish (ASJ) AF: 0.225 AC: 5780 AN: 25720

East Asian (EAS) AF: 0.264 AC: 10406 AN: 39454

South Asian (SAS) AF: 0.250 AC: 21388 AN: 85628

European-Finnish (FIN) AF: 0.0817 AC: 4347 AN: 53206

Middle Eastern (MID) AF: 0.206 AC: 1177 AN: 5726

European-Non Finnish (NFE) AF: 0.159 AC: 176068 AN: 1104172

Other (OTH) AF: 0.179 AC: 10682 AN: 59824

GnomAD4 genome AF: 0.173 AC: 26267 AN: 152234 Hom.: 2461 Cov.: 33 AF XY: 0.174 AC XY: 12982 AN XY: 74432

African (AFR) AF: 0.157 AC: 6530 AN: 41534

American (AMR) AF: 0.264 AC: 4039 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.231 AC: 803 AN: 3470

East Asian (EAS) AF: 0.246 AC: 1272 AN: 5166

South Asian (SAS) AF: 0.266 AC: 1286 AN: 4830

European-Finnish (FIN) AF: 0.0805 AC: 855 AN: 10616

Middle Eastern (MID) AF: 0.228 AC: 67 AN: 294

European-Non Finnish (NFE) AF: 0.160 AC: 10900 AN: 67998

Other (OTH) AF: 0.188 AC: 398 AN: 2114

Alfa AF: 0.171 Hom.: 1539

Bravo AF: 0.185

TwinsUK AF: 0.163 AC: 603

ALSPAC AF: 0.156 AC: 602

ESP6500AA AF: 0.158 AC: 698

ESP6500EA AF: 0.164 AC: 1413

ExAC AF: 0.190 AC: 23117

Asia WGS AF: 0.271 AC: 940 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.24
BayesDel_addAF	Benign	-0.67	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	8.5
DANN	Benign	0.97
DEOGEN2	Benign	0.065	.;.;T;T;T
Eigen	Benign	-0.71
Eigen_PC	Benign	-0.75
FATHMM_MKL	Benign	0.29	N
LIST_S2	Benign	0.57	T;T;.;.;T
MetaRNN	Benign	0.0044	T;T;T;T;T
MetaSVM	Benign	-0.98	T
PhyloP100		0.81
PROVEAN	Benign	0.0	N;.;.;.;.
REVEL	Benign	0.027
Sift	Pathogenic	0.0	D;.;.;.;.
Sift4G	Pathogenic	0.0	D;D;.;.;.
Polyphen		0.0060	B;B;B;B;B
Vest4		0.11
MPC		0.27
ClinPred		0.059	T
GERP RS		-3.6
gMVP		0.15
Mutation Taster		=99/1	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs7513351; hg19: chr1-156213921; COSMIC: COSV52744254; COSMIC: COSV52744254;