1-156243866-C-A

Variant names:

• chr1-156243866-C-A
• rs1186280817
• ENST00000623241.3:c.631G>T

Variant summary

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

The NM_024897.4(PAQR6):​c.1051G>T​(p.Gly351Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000693 in 1,442,012 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/19 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. G351R) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: PAQR6 NM_024897.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.376
• Publications: 0 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: 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=0.19540024).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024897.4. 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
	PAQR6	NM_198406.3	MANE Select	c.*263G>T		3_prime_UTR	Exon 8 of 8	NP_940798.1	Q5TCK7
	PAQR6	NM_024897.4		c.1051G>T	p.Gly351Cys	missense	Exon 7 of 7	NP_079173.2
	PAQR6	NM_001272106.2		c.847G>T	p.Gly283Cys	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.631G>T	p.Gly211Cys	missense	Exon 5 of 5	ENSP00000485607.1	Q7Z4Q8
	PAQR6	ENST00000292291.10	TSL:1 MANE Select	c.*263G>T		3_prime_UTR	Exon 8 of 8	ENSP00000292291.5	Q6TCH4-1
	PAQR6	ENST00000368270.2	TSL:1	c.*263G>T		3_prime_UTR	Exon 7 of 7	ENSP00000357253.1	Q6TCH4-4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.93e-7 AC: 1 AN: 1442012 Hom.: 0 Cov.: 30 AF XY: 0.00000140 AC XY: 1 AN XY: 714064

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 33144

American (AMR) AF: 0.00 AC: 0 AN: 43682

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25158

East Asian (EAS) AF: 0.00 AC: 0 AN: 39314

South Asian (SAS) AF: 0.00 AC: 0 AN: 84684

European-Finnish (FIN) AF: 0.0000190 AC: 1 AN: 52746

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5678

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1098062

Other (OTH) AF: 0.00 AC: 0 AN: 59544

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.23
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	13
DANN	Benign	0.95
DEOGEN2	Benign	0.076	T
Eigen	Benign	-0.32
Eigen_PC	Benign	-0.47
FATHMM_MKL	Benign	0.31	N
LIST_S2	Benign	0.42	T
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.20	T
MetaSVM	Benign	-1.1	T
PhyloP100		0.38
PROVEAN	Benign	-0.53	N
REVEL	Benign	0.061
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.27
MutPred		0.21		Gain of stability (P = 0.0053)
MVP		0.32
MPC		0.26
ClinPred		0.36	T
GERP RS		-0.98
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
gMVP		0.030
Mutation Taster		=97/3	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs1186280817; hg19: chr1-156213657;