Genetic Variant PARD3B:p.Thr171Met (chr2-205104433-C-T) – 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.512C>T(p.Thr171Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000182 in 1,595,546 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000017 ( 0 hom. )

Consequence

PARD3B
NM_001302769.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.32

Publications

2 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:

Genome browser will be placed here

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=0.064611316).

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.512C>T	p.Thr171Met	missense	Exon 5 of 23	NP_001289698.1	Q8TEW8-1
PARD3B	NM_152526.6		c.512C>T	p.Thr171Met	missense	Exon 5 of 22	NP_689739.4
PARD3B	NM_057177.7		c.512C>T	p.Thr171Met	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.512C>T	p.Thr171Met	missense	Exon 5 of 23	ENSP00000385848.2	Q8TEW8-1
PARD3B	ENST00000358768.6	TSL:1	c.512C>T	p.Thr171Met	missense	Exon 5 of 22	ENSP00000351618.2	Q8TEW8-2
PARD3B	ENST00000351153.5	TSL:1	c.512C>T	p.Thr171Met	missense	Exon 5 of 22	ENSP00000317261.2	Q8TEW8-6

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152212

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000482

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:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000161

AC:

AN:

249030

AF XY:

0.0000148

show subpopulations

Gnomad AFR exome

AF:

0.0000646

Gnomad AMR exome

AF:

0.0000290

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000177

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000173

AC:

AN:

1443216

Hom.:

Cov.:

AF XY:

0.0000195

AC XY:

AN XY:

719088

show subpopulations

African (AFR)

AF:

0.000151

AC:

AN:

33014

American (AMR)

AF:

0.0000224

AC:

AN:

44670

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26022

East Asian (EAS)

AF:

0.0000506

AC:

AN:

39524

South Asian (SAS)

AF:

0.00

AC:

AN:

85812

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53260

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5734

European-Non Finnish (NFE)

AF:

0.0000155

AC:

AN:

1095422

Other (OTH)

AF:

0.00

AC:

AN:

59758

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.423

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

AF:

0.0000263

AC:

AN:

152330

Hom.:

Cov.:

AF XY:

0.0000268

AC XY:

AN XY:

74490

show subpopulations

African (AFR)

AF:

0.0000481

AC:

AN:

41590

American (AMR)

AF:

0.00

AC:

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5188

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000294

AC:

AN:

68016

Other (OTH)

AF:

0.00

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.538

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000416

ESP6500AA

AF:

0.000269

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000166

AC:

EpiCase

AF:

0.000109

EpiControl

AF:

0.00

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.076

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.67

CADD

Benign

(source)

DANN

Benign

0.58

DEOGEN2

Benign

0.0036

Eigen

Benign

-0.62

Eigen_PC

Benign

-0.56

FATHMM_MKL

Benign

0.37

LIST_S2

Benign

0.80

M_CAP

Benign

0.0040

MetaRNN

Benign

0.065

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.6

PhyloP100

1.3

PrimateAI

Benign

0.33

PROVEAN

Benign

-1.6

REVEL

Benign

0.015

Sift

Benign

0.064

Sift4G

Benign

0.12

Polyphen

0.13

Vest4

0.18

MVP

0.43

MPC

0.024

ClinPred

0.040

GERP RS

1.4

Varity_R

0.023

gMVP

0.20

Mutation Taster

=98/2

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over