Genetic Variant PARD3B:p.Arg192Thr (chr2-205104496-G-C) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001302769.2(PARD3B):c.575G>C(p.Arg192Thr) variant causes a missense 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

PARD3B
NM_001302769.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.250

Publications

34 publications found

Variant links:

Genes affected

PARD3B (HGNC:14446): (par-3 family cell polarity regulator beta) Predicted to enable phosphatidylinositol binding activity. Predicted to be involved in several processes, including establishment of cell polarity; establishment of centrosome localization; and establishment or maintenance of epithelial cell apical/basal polarity. Located in cell junction. Part of protein-containing complex. [provided by Alliance of Genome Resources, Apr 2022]

PARD3B links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.059224218).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001302769.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PARD3B	NM_001302769.2	MANE Select	c.575G>C	p.Arg192Thr	missense	Exon 5 of 23	NP_001289698.1	Q8TEW8-1
PARD3B	NM_152526.6		c.575G>C	p.Arg192Thr	missense	Exon 5 of 22	NP_689739.4
PARD3B	NM_057177.7		c.575G>C	p.Arg192Thr	missense	Exon 5 of 22	NP_476518.4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PARD3B	ENST00000406610.7	TSL:1 MANE Select	c.575G>C	p.Arg192Thr	missense	Exon 5 of 23	ENSP00000385848.2	Q8TEW8-1
PARD3B	ENST00000358768.6	TSL:1	c.575G>C	p.Arg192Thr	missense	Exon 5 of 22	ENSP00000351618.2	Q8TEW8-2
PARD3B	ENST00000351153.5	TSL:1	c.575G>C	p.Arg192Thr	missense	Exon 5 of 22	ENSP00000317261.2	Q8TEW8-6

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

1417464

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

707516

African (AFR)

AF:

0.00

AC:

AN:

32474

American (AMR)

AF:

0.00

AC:

AN:

44628

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25912

East Asian (EAS)

AF:

0.00

AC:

AN:

39400

South Asian (SAS)

AF:

0.00

AC:

AN:

85246

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53220

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5686

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1072008

Other (OTH)

AF:

0.00

AC:

AN:

58890

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.086

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.66

CADD

Benign

4.8

(source)

DANN

Benign

0.25

DEOGEN2

Benign

0.00087

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.026

LIST_S2

Benign

0.13

M_CAP

Benign

0.0054

MetaRNN

Benign

0.059

MetaSVM

Benign

-0.95

MutationAssessor

Benign

1.2

PhyloP100

0.25

PrimateAI

Benign

0.35

PROVEAN

Benign

-0.56

REVEL

Benign

0.014

Sift

Benign

0.24

Sift4G

Benign

0.48

Polyphen

0.0090

Vest4

0.17

MutPred

0.27

Gain of glycosylation at R192 (P = 0.0315)

MVP

0.16

MPC

0.026

ClinPred

0.067

GERP RS

0.10

Varity_R

0.042

gMVP

0.24

Mutation Taster

=91/9

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over