4-78926529-T-C

Variant names:

• chr4-78926529-T-C
• rs759288681
• NM_001040202.2:c.694A>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001040202.2(PAQR3):​c.694A>G​(p.Ile232Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000131 in 1,607,526 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000067 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000014 (0 hom.)
• Consequence: PAQR3 NM_001040202.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.61
• Publications: 1 publications found

Genes affected

PAQR3 (HGNC:30130): (progestin and adipoQ receptor family member 3) This gene encodes a seven-transmembrane protein localized in the Golgi apparatus in mammalian cells. The encoded protein belongs to the progestin and adipoQ receptor (PAQR) family. This protein functions as a tumor suppressor by inhibiting the Raf/MEK/ERK signaling cascade. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Apr 2017]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.18971175).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001040202.2. 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
	PAQR3	NM_001040202.2	MANE Select	c.694A>G	p.Ile232Val	missense	Exon 4 of 6	NP_001035292.1	Q6TCH7-1
	PAQR3	NM_001350105.2		c.340A>G	p.Ile114Val	missense	Exon 4 of 6	NP_001337034.1
	PAQR3	NM_001350106.2		c.340A>G	p.Ile114Val	missense	Exon 5 of 7	NP_001337035.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PAQR3	ENST00000512733.5	TSL:1 MANE Select	c.694A>G	p.Ile232Val	missense	Exon 4 of 6	ENSP00000421981.1	Q6TCH7-1
	PAQR3	ENST00000342820.10	TSL:1	n.694A>G		non_coding_transcript_exon	Exon 4 of 13	ENSP00000344203.6	F8W784
	PAQR3	ENST00000395594.2	TSL:1	n.694A>G		non_coding_transcript_exon	Exon 4 of 7	ENSP00000378959.2	Q6TCH7-3

Frequencies

GnomAD3 genomes AF: 0.00000666 AC: 1 AN: 150144 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000148

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000199 AC: 5 AN: 251332 AF XY: 0.0000147

Gnomad AFR exome AF: 0.0000615

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000264

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000137 AC: 20 AN: 1457382 Hom.: 0 Cov.: 31 AF XY: 0.0000124 AC XY: 9 AN XY: 725314

African (AFR) AF: 0.0000899 AC: 3 AN: 33378

American (AMR) AF: 0.00 AC: 0 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26108

East Asian (EAS) AF: 0.00 AC: 0 AN: 39682

South Asian (SAS) AF: 0.00 AC: 0 AN: 86188

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53410

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5754

European-Non Finnish (NFE) AF: 0.0000153 AC: 17 AN: 1107886

Other (OTH) AF: 0.00 AC: 0 AN: 60260

GnomAD4 genome AF: 0.00000666 AC: 1 AN: 150144 Hom.: 0 Cov.: 32 AF XY: 0.0000137 AC XY: 1 AN XY: 73196

African (AFR) AF: 0.00 AC: 0 AN: 40960

American (AMR) AF: 0.00 AC: 0 AN: 15082

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3462

East Asian (EAS) AF: 0.00 AC: 0 AN: 5158

South Asian (SAS) AF: 0.00 AC: 0 AN: 4794

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9716

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 310

European-Non Finnish (NFE) AF: 0.0000148 AC: 1 AN: 67690

Other (OTH) AF: 0.00 AC: 0 AN: 2062

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ExAC AF: 0.0000165 AC: 2

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.077
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	18
DANN	Benign	0.52
DEOGEN2	Benign	0.24	T
Eigen	Benign	-0.32
Eigen_PC	Benign	-0.13
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.85	T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.19	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.55	N
PhyloP100		4.6
PrimateAI	Benign	0.41	T
PROVEAN	Benign	-0.40	N
REVEL	Benign	0.11
Sift	Benign	0.44	T
Sift4G	Benign	0.55	T
Polyphen		0.0010	B
Vest4		0.40
MutPred		0.51		Loss of helix (P = 0.0558)
MVP		0.055
MPC		0.095
ClinPred		0.070	T
GERP RS		5.7
Varity_R		0.062
gMVP		0.63
Mutation Taster		=84/16	polymorphism

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: rs759288681; hg19: chr4-79847683;