Genetic Variant PARD3B:p.Thr27Ile (chr2-204546079-C-T) – 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_001302769.2(PARD3B):c.80C>T(p.Thr27Ile) 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. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

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

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.24

Publications

0 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: 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=0.113758594).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PARD3B	NM_001302769.2 link	c.80C>T	p.Thr27Ile	missense_variant	Exon 1 of 23	ENST00000406610.7	NP_001289698.1	Q8TEW8-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PARD3B	ENST00000406610.7 link	c.80C>T	p.Thr27Ile	missense_variant	Exon 1 of 23	1	NM_001302769.2	ENSP00000385848.2		Q8TEW8-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1406534

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

694744

African (AFR)

AF:

0.00

AC:

AN:

31882

American (AMR)

AF:

0.00

AC:

AN:

37728

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25236

East Asian (EAS)

AF:

0.00

AC:

AN:

36194

South Asian (SAS)

AF:

0.00

AC:

AN:

79956

European-Finnish (FIN)

AF:

0.00

AC:

AN:

48424

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5706

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1083150

Other (OTH)

AF:

0.00

AC:

AN:

58258

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

May 14, 2025

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.80C>T (p.T27I) alteration is located in exon 1 (coding exon 1) of the PARD3B gene. This alteration results from a C to T substitution at nucleotide position 80, causing the threonine (T) at amino acid position 27 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.19

BayesDel_addAF

Benign

-0.093

BayesDel_noAF

Benign

-0.37

CADD

Benign

(source)

DANN

Benign

0.94

DEOGEN2

Benign

0.0010

T;T;.;.;.

Eigen

Benign

-0.21

Eigen_PC

Benign

-0.032

FATHMM_MKL

Benign

0.67

LIST_S2

Benign

0.77

T;T;T;T;T

M_CAP

Benign

0.024

MetaRNN

Benign

0.11

T;T;T;T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

-0.69

N;.;N;N;N

PhyloP100

1.2

PrimateAI

Pathogenic

0.86

PROVEAN

Benign

0.030

N;.;N;N;N

REVEL

Benign

0.11

Sift

Benign

1.0

T;.;T;T;T

Sift4G

Benign

1.0

T;T;T;T;T

Polyphen

0.87

P;.;B;.;P

Vest4

0.24

MutPred

0.29

Loss of disorder (P = 0.0781);Loss of disorder (P = 0.0781);Loss of disorder (P = 0.0781);Loss of disorder (P = 0.0781);Loss of disorder (P = 0.0781);

MVP

0.55

MPC

0.026

ClinPred

0.49

GERP RS

5.1

PromoterAI

-0.0099

Neutral

(source)

Varity_R

0.13

gMVP

0.21

Mutation Taster

=93/7

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

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over