Variant chr10-34119721-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2

The NM_001184785.2(PARD3):c.3560C>T(p.Thr1187Met) variant causes a missense change. The variant allele was found at a frequency of 0.0012 in 1,611,664 control chromosomes in the GnomAD database, including 16 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.0063 ( 9 hom., cov: 33)

Exomes 𝑓: 0.00067 ( 7 hom. )

Consequence

PARD3
NM_001184785.2 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 3.93

Variant links:

Genes affected

PARD3 (HGNC:16051): (par-3 family cell polarity regulator) This gene encodes a member of the PARD protein family. PARD family members interact with other PARD family members and other proteins; they affect asymmetrical cell division and direct polarized cell growth. Multiple alternatively spliced transcript variants have been described for this gene. [provided by RefSeq, Oct 2011]

PARD3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0062744617).

BP6

Variant 10-34119721-G-A is Benign according to our data. Variant chr10-34119721-G-A is described in ClinVar as [Benign]. Clinvar id is 3039204.Status of the report is no_assertion_criteria_provided, 0 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00634 (965/152324) while in subpopulation AFR AF= 0.0214 (890/41568). AF 95% confidence interval is 0.0202. There are 9 homozygotes in gnomad4. There are 459 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High AC in GnomAd4 at 965 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PARD3	NM_001184785.2 linkuse as main transcript	c.3560C>T	p.Thr1187Met	missense_variant	24/25	ENST00000374788.8	NP_001171714.1	Q8TEW0-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PARD3	ENST00000374788.8 linkuse as main transcript	c.3560C>T	p.Thr1187Met	missense_variant	24/25	1	NM_001184785.2	ENSP00000363920.3		Q8TEW0-2

Frequencies

GnomAD3 genomes

AF:

0.00633

AC:

964

AN:

152208

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0214

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00366

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00765

GnomAD3 exomes

AF:

0.00167

AC:

413

AN:

246686

Hom.:

AF XY:

0.00124

AC XY:

166

AN XY:

134096

show subpopulations

Gnomad AFR exome

AF:

0.0225

Gnomad AMR exome

AF:

0.00145

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:

0.0000361

Gnomad OTH exome

AF:

0.00116

GnomAD4 exome

AF:

0.000667

AC:

973

AN:

1459340

Hom.:

Cov.:

AF XY:

0.000551

AC XY:

400

AN XY:

725670

show subpopulations

Gnomad4 AFR exome

AF:

0.0217

Gnomad4 AMR exome

AF:

0.00166

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000702

Gnomad4 OTH exome

AF:

0.00144

GnomAD4 genome

AF:

0.00634

AC:

965

AN:

152324

Hom.:

Cov.:

AF XY:

0.00616

AC XY:

459

AN XY:

74484

show subpopulations

Gnomad4 AFR

AF:

0.0214

Gnomad4 AMR

AF:

0.00366

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00757

Alfa

AF:

0.00117

Hom.:

Bravo

AF:

0.00726

ESP6500AA

AF:

0.0213

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.00190

AC:

231

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.0000546

EpiControl

AF:

0.00

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

PARD3-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jun 06, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.091

BayesDel_addAF

Benign

-0.68

BayesDel_noAF

Benign

-0.74

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.17

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

Eigen

Benign

-0.34

Eigen_PC

Benign

-0.34

FATHMM_MKL

Benign

0.75

LIST_S2

Uncertain

0.89

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

MetaRNN

Benign

0.0063

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

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

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

PrimateAI

Benign

0.36

PROVEAN

Benign

-1.5

N;N;N;N;N;N;N;N

REVEL

Benign

0.099

Sift

Uncertain

0.021

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

Sift4G

Uncertain

0.060

T;D;D;D;T;T;T;D

Polyphen

0.48

P;.;P;P;P;P;P;.

Vest4

0.22

MVP

0.26

MPC

0.13

ClinPred

0.023

GERP RS

3.5

Varity_R

0.035

gMVP

0.12

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