15-69399974-C-G

Variant summary

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

The NM_017705.4(PAQR5):c.610C>G(p.Leu204Val) variant causes a missense, splice region 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. 16/22 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: PAQR5 NM_017705.4 missense, splice_region
• Scores: Splicing: ADA: 0.0009736
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.474

Genes affected

PAQR5 (HGNC:29645): (progestin and adipoQ receptor family member 5) Predicted to enable signaling receptor activity. Predicted to be involved in oogenesis. Predicted to be located in plasma membrane. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

KIF23-AS1 (HGNC:27075): (KIF23 and PAQR5 antisense RNA 1)

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=0.12823543).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PAQR5	NM_017705.4	c.610C>G	p.Leu204Val	missense_variant, splice_region_variant	8/9	ENST00000395407.7
KIF23-AS1	NR_132971.1	n.879-2226G>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PAQR5	ENST00000395407.7	c.610C>G	p.Leu204Val	missense_variant, splice_region_variant	8/9	1	NM_017705.4	P1
KIF23-AS1	ENST00000558617.1	n.933+999G>C		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

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

Jan 10, 2023

The c.610C>G (p.L204V) alteration is located in exon 8 (coding exon 6) of the PAQR5 gene. This alteration results from a C to G substitution at nucleotide position 610, causing the leucine (L) at amino acid position 204 to be replaced by a valine (V). 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	Benign	0.10
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.59
Cadd	Benign	18
Dann	Benign	0.97
DEOGEN2	Benign	0.036	T;T;T
Eigen	Benign	-0.25
Eigen_PC	Benign	-0.10
FATHMM_MKL	Benign	0.72	D
M_CAP	Benign	0.0056	T
MetaRNN	Benign	0.13	T;T;T
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-1.0	N;N;N
REVEL	Benign	0.029
Sift	Benign	0.37	T;T;T
Sift4G	Benign	0.64	T;T;T
Polyphen		0.010	B;B;B
Vest4		0.28
MutPred		0.48		Loss of stability (P = 0.0591);Loss of stability (P = 0.0591);Loss of stability (P = 0.0591);
MVP		0.28
MPC		0.23
ClinPred		0.15	T
GERP RS		2.7
Varity_R		0.093
gMVP		0.36

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00097
dbscSNV1_RF	Benign	0.12
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: chr15-69692313;