1-156244799-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 3P and 1B. PM2PP3BP4

The ENST00000292291.10(PAQR6):​c.722T>C​(p.Leu241Pro) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Consequence

PAQR6
ENST00000292291.10 missense

Scores

4
3
5

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.25
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
Multiple lines of computational evidence support a deleterious effect 6: AlphaMissense, BayesDel_addAF, BayesDel_noAF, Cadd, Eigen, phyloP100way_vertebrate [when max_spliceai, M_CAP, MetaRNN, MutationTaster was below the threshold]
BP4
Computational evidence support a benign effect (MetaRNN=0.37583834).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
PAQR6NM_198406.3 linkuse as main transcriptc.722T>C p.Leu241Pro missense_variant 7/8 ENST00000292291.10 NP_940798.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
PAQR6ENST00000292291.10 linkuse as main transcriptc.722T>C p.Leu241Pro missense_variant 7/81 NM_198406.3 ENSP00000292291 P4Q6TCH4-1

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
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsDec 07, 2023The c.404T>C (p.L135P) alteration is located in exon 6 (coding exon 4) of the PAQR6 gene. This alteration results from a T to C substitution at nucleotide position 404, causing the leucine (L) at amino acid position 135 to be replaced by a proline (P). 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
AlphaMissense
Pathogenic
0.96
BayesDel_addAF
Pathogenic
0.39
D
BayesDel_noAF
Pathogenic
0.18
CADD
Pathogenic
30
DANN
Uncertain
1.0
DEOGEN2
Benign
0.0097
T;T;T
Eigen
Pathogenic
0.72
Eigen_PC
Uncertain
0.64
FATHMM_MKL
Uncertain
0.90
D
LIST_S2
Benign
0.15
.;.;T
M_CAP
Benign
0.064
D
MetaRNN
Benign
0.38
T;T;T
MutationTaster
Benign
1.0
D;D;D;D;D;D
Polyphen
0.99
D;D;D
Vest4
0.43
MVP
0.34
ClinPred
1.0
D
GERP RS
4.9

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.080
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: chr1-156214590; API