Variant 2-205104487-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001302769.2(PARD3B):c.566C>G(p.Thr189Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000139 in 1,437,294 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

PARD3B
NM_001302769.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.185

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 made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.061965942).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PARD3B	NM_001302769.2 link	c.566C>G	p.Thr189Ser	missense_variant	Exon 5 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.566C>G	p.Thr189Ser	missense_variant	Exon 5 of 23	1	NM_001302769.2	ENSP00000385848.2		Q8TEW8-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000139

AC:

AN:

1437294

Hom.:

Cov.:

AF XY:

0.00000279

AC XY:

AN XY:

716316

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000168

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

Oct 25, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.566C>G (p.T189S) alteration is located in exon 5 (coding exon 5) of the PARD3B gene. This alteration results from a C to G substitution at nucleotide position 566, causing the threonine (T) at amino acid position 189 to be replaced by a serine (S). 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

0.079

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.80

CADD

Benign

2.6

DANN

Benign

0.43

DEOGEN2

Benign

0.00087

T;T;.;.;.;.;.;T

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.064

LIST_S2

Benign

0.49

T;T;T;T;T;T;T;T

M_CAP

Benign

0.0048

MetaRNN

Benign

0.062

T;T;T;T;T;T;T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

0.92

L;.;L;L;L;.;.;.

PrimateAI

Benign

0.31

PROVEAN

Benign

0.19

N;.;N;N;N;.;.;.

REVEL

Benign

0.022

Sift

Benign

0.61

T;.;T;T;T;.;.;.

Sift4G

Benign

0.85

T;T;T;T;T;T;T;T

Polyphen

0.0040

B;.;B;.;B;.;.;.

Vest4

0.093

MutPred

0.16

Gain of phosphorylation at S190 (P = 0.1367);Gain of phosphorylation at S190 (P = 0.1367);Gain of phosphorylation at S190 (P = 0.1367);Gain of phosphorylation at S190 (P = 0.1367);Gain of phosphorylation at S190 (P = 0.1367);.;.;.;

MVP

0.33

MPC

0.022

ClinPred

0.034

GERP RS

2.4

Varity_R

0.053

gMVP

0.12

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over