16-2969783-G-C

Variant names:

• chr16-2969783-G-C
• rs777226428
• NM_152341.5:c.109G>C

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_152341.5(PAQR4):​c.109G>C​(p.Gly37Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts 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. G37S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PAQR4 NM_152341.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.15
• Publications: 0 publications found

Genes affected

PAQR4 (HGNC:26386): (progestin and adipoQ receptor family member 4) Predicted to enable signaling receptor activity. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

PKMYT1 (HGNC:29650): (protein kinase, membrane associated tyrosine/threonine 1) This gene encodes a member of the serine/threonine protein kinase family. The encoded protein is a membrane-associated kinase that negatively regulates the G2/M transition of the cell cycle by phosphorylating and inactivating cyclin-dependent kinase 1. The activity of the encoded protein is regulated by polo-like kinase 1. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, May 2012]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.32691926).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152341.5. 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
	PAQR4	NM_152341.5	MANE Select	c.109G>C	p.Gly37Arg	missense	Exon 1 of 3	NP_689554.2
	PAQR4	NM_001284511.2		c.109G>C	p.Gly37Arg	missense	Exon 1 of 3	NP_001271440.1	Q8N4S7-2
	PAQR4	NM_001324118.2		c.109G>C	p.Gly37Arg	missense	Exon 1 of 4	NP_001311047.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PAQR4	ENST00000318782.9	TSL:1 MANE Select	c.109G>C	p.Gly37Arg	missense	Exon 1 of 3	ENSP00000321804.8	Q8N4S7-1
	PAQR4	ENST00000293978.12	TSL:2	c.109G>C	p.Gly37Arg	missense	Exon 1 of 3	ENSP00000293978.8	Q8N4S7-2
	PAQR4	ENST00000896898.1		c.109G>C	p.Gly37Arg	missense	Exon 1 of 3	ENSP00000566957.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000463 AC: 1 AN: 216144 AF XY: 0.00000830

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 FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000108

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1450334 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 721100

African (AFR) AF: 0.00 AC: 0 AN: 32918

American (AMR) AF: 0.00 AC: 0 AN: 43616

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25956

East Asian (EAS) AF: 0.00 AC: 0 AN: 38822

South Asian (SAS) AF: 0.00 AC: 0 AN: 85466

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50214

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5716

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1107830

Other (OTH) AF: 0.00 AC: 0 AN: 59796

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.30
BayesDel_addAF	Benign	0.0031	T
BayesDel_noAF	Benign	-0.23
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.016	T
Eigen	Benign	-0.026
Eigen_PC	Benign	0.077
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.93	D
M_CAP	Uncertain	0.27	D
MetaRNN	Benign	0.33	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.55	N
PhyloP100		7.2
PrimateAI	Pathogenic	0.84	D
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.089
Sift	Benign	0.092	T
Sift4G	Benign	0.32	T
Polyphen		0.95	P
Vest4		0.36
MutPred		0.47		Gain of methylation at G37 (P = 0.0321)
MVP		0.21
MPC		0.31
ClinPred		0.76	D
GERP RS		4.5
PromoterAI		-0.049	Neutral
Varity_R		0.20
gMVP		0.71

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

Other links and lift over

dbSNP: rs777226428; hg19: chr16-3019784;