ENST00000623241.3:c.367G>A

Variant names:

• chr1-156244130-C-T
• rs7513351
• ENST00000623241.3:c.367G>A
• PAQR6 p.Glu123Lys

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000623241.3. 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
	PAQR6	NM_198406.3	MANE Select	c.1034G>A	p.Ter345Ter	stop_retained	Exon 8 of 8	NP_940798.1	Q5TCK7
	PAQR6	NM_024897.4		c.787G>A	p.Glu263Lys	missense	Exon 7 of 7	NP_079173.2
	PAQR6	NM_001272106.2		c.583G>A	p.Glu195Lys	missense	Exon 6 of 6	NP_001259035.1	B4DJ42

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PAQR6	ENST00000623241.3	TSL:1	c.367G>A	p.Glu123Lys	missense	Exon 5 of 5	ENSP00000485607.1	Q7Z4Q8
	PAQR6	ENST00000292291.10	TSL:1 MANE Select	c.1034G>A	p.Ter345Ter	stop_retained	Exon 8 of 8	ENSP00000292291.5	Q6TCH4-1
	PAQR6	ENST00000368270.2	TSL:1	c.962G>A	p.Ter321Ter	stop_retained	Exon 7 of 7	ENSP00000357253.1	Q6TCH4-4

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

Asia WGS AF: 0.271 AC: 940 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

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
Eigen	Benign	-0.71
Eigen_PC	Benign	-0.75
FATHMM_MKL	Benign	0.29	N
LIST_S2	Benign	0.57	T
MetaRNN	Benign	0.0044	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
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs7513351;

hg19: chr1-156213921;

COSMIC: COSV52744254;

COSMIC: COSV52744254;