Genetic Variant NM_001040202.2:c.694A>C (chr4-78926529-T-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001040202.2(PAQR3):c.694A>C(p.Ile232Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000000686 in 1,457,382 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict 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. I232V) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

PAQR3
NM_001040202.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.61

Publications

0 publications found

Variant links:

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]

PAQR3 links:

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ACMG classification

Classification was made for transcript

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=0.19251767).

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PAQR3	NM_001040202.2	MANE Select	c.694A>C	p.Ile232Leu	missense	Exon 4 of 6	NP_001035292.1	Q6TCH7-1
PAQR3	NM_001350105.2		c.340A>C	p.Ile114Leu	missense	Exon 4 of 6	NP_001337034.1
PAQR3	NM_001350106.2		c.340A>C	p.Ile114Leu	missense	Exon 5 of 7	NP_001337035.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PAQR3	ENST00000512733.5	TSL:1 MANE Select	c.694A>C	p.Ile232Leu	missense	Exon 4 of 6	ENSP00000421981.1	Q6TCH7-1
PAQR3	ENST00000342820.10	TSL:1	n.694A>C		non_coding_transcript_exon	Exon 4 of 13	ENSP00000344203.6	F8W784
PAQR3	ENST00000395594.2	TSL:1	n.694A>C		non_coding_transcript_exon	Exon 4 of 7	ENSP00000378959.2	Q6TCH7-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.86e-7

AC:

AN:

1457382

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

725314

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33378

American (AMR)

AF:

0.00

AC:

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26108

East Asian (EAS)

AF:

0.00

AC:

AN:

39682

South Asian (SAS)

AF:

0.00

AC:

AN:

86188

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53410

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5754

European-Non Finnish (NFE)

AF:

9.03e-7

AC:

AN:

1107886

Other (OTH)

AF:

0.00

AC:

AN:

60260

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.49

CADD

Benign

(source)

DANN

Benign

0.81

DEOGEN2

Benign

0.22

Eigen

Benign

-0.35

Eigen_PC

Benign

-0.16

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Benign

0.82

M_CAP

Benign

0.013

MetaRNN

Benign

0.19

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.36

PhyloP100

4.6

PrimateAI

Uncertain

0.49

PROVEAN

Benign

-0.42

REVEL

Benign

0.13

Sift

Benign

0.62

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.33

MutPred

0.49

Gain of catalytic residue at I232 (P = 0.0596)

MVP

0.076

MPC

0.11

ClinPred

0.44

GERP RS

5.7

Varity_R

0.14

gMVP

0.75

Mutation Taster

=71/29

polymorphism

(source)

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over