Variant 2-205113512-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001302769.2(PARD3B):c.615G>T(p.Glu205Asp) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,198 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

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: 4.10

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 Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.3851565).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PARD3B	NM_001302769.2 linkuse as main transcript	c.615G>T	p.Glu205Asp	missense_variant	6/23	ENST00000406610.7	NP_001289698.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PARD3B	ENST00000406610.7 linkuse as main transcript	c.615G>T	p.Glu205Asp	missense_variant	6/23	1	NM_001302769.2	ENSP00000385848	P1	Q8TEW8-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000804

AC:

AN:

248668

Hom.:

AF XY:

0.00000741

AC XY:

AN XY:

134948

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000584

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461198

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726902

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000448

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:

0.00

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

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 08, 2022

The c.615G>T (p.E205D) alteration is located in exon 6 (coding exon 6) of the PARD3B gene. This alteration results from a G to T substitution at nucleotide position 615, causing the glutamic acid (E) at amino acid position 205 to be replaced by an aspartic acid (D). 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

0.18

BayesDel_addAF

Benign

-0.077

BayesDel_noAF

Benign

-0.35

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.11

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

Eigen

Uncertain

0.60

Eigen_PC

Uncertain

0.56

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.83

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

M_CAP

Benign

0.012

MetaRNN

Benign

0.39

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

MetaSVM

Benign

-0.93

MutationAssessor

Uncertain

2.5

M;.;M;M;M;.;.;.

MutationTaster

Benign

0.97

D;D;D;D

PrimateAI

Uncertain

0.62

PROVEAN

Uncertain

-2.8

D;.;D;D;D;.;.;.

REVEL

Benign

0.16

Sift

Uncertain

0.0050

D;.;D;D;D;.;.;.

Sift4G

Uncertain

0.0050

D;D;D;D;D;D;D;D

Polyphen

1.0

D;.;D;.;D;.;.;.

Vest4

0.23

MutPred

0.29

Loss of glycosylation at S207 (P = 0.1108);Loss of glycosylation at S207 (P = 0.1108);Loss of glycosylation at S207 (P = 0.1108);Loss of glycosylation at S207 (P = 0.1108);Loss of glycosylation at S207 (P = 0.1108);.;.;.;

MVP

0.66

MPC

0.024

ClinPred

0.88

GERP RS

4.6

Varity_R

0.58

gMVP

0.52

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over