1-156244207-G-T

Position:

• chr1-156244207-G-T

Variant summary

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

The ENST00000623241.3(PAQR6):​c.290C>A​(p.Pro97His) 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. 12/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: PAQR6 ENST00000623241.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0880

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=0.19166005).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PAQR6	NM_198406.3	c.957C>A	p.Thr319=	synonymous_variant	8/8	ENST00000292291.10	NP_940798.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PAQR6	ENST00000292291.10	c.957C>A	p.Thr319=	synonymous_variant	8/8	1	NM_198406.3	ENSP00000292291	P4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 25, 2022

The c.710C>A (p.P237H) alteration is located in exon 7 (coding exon 5) of the PAQR6 gene. This alteration results from a C to A substitution at nucleotide position 710, causing the proline (P) at amino acid position 237 to be replaced by a histidine (H). 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	-0.22	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	3.2
DANN	Benign	0.95
DEOGEN2	Benign	0.067	.;.;T;T;T
Eigen	Benign	-0.078
Eigen_PC	Benign	-0.25
FATHMM_MKL	Benign	0.51	D
LIST_S2	Benign	0.36	T;T;.;.;T
M_CAP	Benign	0.022	T
MetaRNN	Benign	0.19	T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	1.0	N;N;N;N;N;N
PROVEAN	Benign	-0.41	N;.;.;.;.
REVEL	Benign	0.057
Sift	Uncertain	0.0010	D;.;.;.;.
Sift4G	Pathogenic	0.0	D;D;.;.;.
Polyphen		1.0	D;D;D;D;D
Vest4		0.17
MutPred		0.26		Loss of relative solvent accessibility (P = 0.0676);.;.;.;.;
MVP		0.49
MPC		0.28
ClinPred		0.24	T
GERP RS		1.8
gMVP		0.24

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-156213998;