chr4-78935171-C-T

Variant names:

• chr4-78935171-C-T
• rs1426788463
• NM_001040202.2:c.298G>A

Variant summary

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

The NM_001040202.2(PAQR3):​c.298G>A​(p.Ala100Thr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: PAQR3 NM_001040202.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.05
• Publications: 0 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.298G>A	p.Ala100Thr	missense	Exon 2 of 6	NP_001035292.1	Q6TCH7-1
	PAQR3	NM_001350105.2		c.-57G>A		5_prime_UTR	Exon 2 of 6	NP_001337034.1
	PAQR3	NM_001350106.2		c.-131G>A		5_prime_UTR	Exon 2 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.298G>A	p.Ala100Thr	missense	Exon 2 of 6	ENSP00000421981.1	Q6TCH7-1
	PAQR3	ENST00000342820.10	TSL:1	n.298G>A		non_coding_transcript_exon	Exon 2 of 13	ENSP00000344203.6	F8W784
	PAQR3	ENST00000395594.2	TSL:1	n.298G>A		non_coding_transcript_exon	Exon 2 of 7	ENSP00000378959.2	Q6TCH7-3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

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	Pathogenic	0.66
BayesDel_addAF	Uncertain	0.034	T
BayesDel_noAF	Benign	-0.19
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.38	T
Eigen	Uncertain	0.55
Eigen_PC	Uncertain	0.58
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.95	D
M_CAP	Benign	0.018	T
MetaRNN	Uncertain	0.69	D
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.6	M
PhyloP100		6.1
PrimateAI	Uncertain	0.69	T
PROVEAN	Benign	-2.2	N
REVEL	Benign	0.15
Sift	Benign	0.083	T
Sift4G	Benign	0.073	T
Polyphen		0.90	P
Vest4		0.72
MutPred		0.52		Gain of helix (P = 0.132)
MVP		0.52
MPC		0.25
ClinPred		0.95	D
GERP RS		5.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.17
gMVP		0.79
Mutation Taster		=13/87	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs1426788463; hg19: chr4-79856325;