chr1-156243866-C-G

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_024897.4(PAQR6):​c.1051G>C​(p.Gly351Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000485 in 1,442,016 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000049 (0 hom.)
• Consequence: PAQR6 NM_024897.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.376

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1719692).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PAQR6	NM_198406.3	c.*263G>C		3_prime_UTR_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	c.*263G>C		3_prime_UTR_variant	Exon 8 of 8	1	NM_198406.3	ENSP00000292291.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000413 AC: 1 AN: 242422 Hom.: 0 AF XY: 0.00000765 AC XY: 1 AN XY: 130642

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000914

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000485 AC: 7 AN: 1442016 Hom.: 0 Cov.: 30 AF XY: 0.00000560 AC XY: 4 AN XY: 714068

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000637

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Sep 04, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1051G>C (p.G351R) alteration is located in exon 7 (coding exon 5) of the PAQR6 gene. This alteration results from a G to C substitution at nucleotide position 1051, causing the glycine (G) at amino acid position 351 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	12
DANN	Uncertain	0.98
DEOGEN2	Benign	0.076	.;.;T;T;T
Eigen	Benign	-0.33
Eigen_PC	Benign	-0.48
FATHMM_MKL	Benign	0.29	N
LIST_S2	Benign	0.53	T;T;.;.;T
M_CAP	Benign	0.020	T
MetaRNN	Benign	0.17	T;T;T;T;T
MetaSVM	Benign	-1.1	T
PROVEAN	Benign	-0.47	N;.;.;.;.
REVEL	Benign	0.052
Sift	Pathogenic	0.0	D;.;.;.;.
Sift4G	Pathogenic	0.0	D;D;.;.;.
Polyphen		0.98	D;D;D;D;D
Vest4		0.20
MutPred		0.31		Gain of solvent accessibility (P = 0.0037);.;.;.;.;
MVP		0.25
MPC		0.29
ClinPred		0.29	T
GERP RS		-0.98
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
gMVP		0.015

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

Publications

LitVar

Other links and lift over

dbSNP: rs1186280817; hg19: chr1-156213657;