dbSNP rs781461462: PARD3:p.Pro910Leu (chr10-34331221-G-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM5BS2

The NM_001184785.2(PARD3):c.2729C>T(p.Pro910Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000198 in 1,461,806 control chromosomes in the GnomAD database, including 1 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P910Q) has been classified as Pathogenic.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000020 ( 1 hom. )

Consequence

PARD3
NM_001184785.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 10.0

Publications

2 publications found

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 was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM5

Other missense variant is known to change same aminoacid residue: Variant chr10-34331221-G-T is described in ClinVar as [Pathogenic]. Clinvar id is 254185.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High AC in GnomAdExome4 at 29 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PARD3	NM_001184785.2 link	c.2729C>T	p.Pro910Leu	missense_variant	Exon 19 of 25	ENST00000374788.8	NP_001171714.1	Q8TEW0-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PARD3	ENST00000374788.8 link	c.2729C>T	p.Pro910Leu	missense_variant	Exon 19 of 25	1	NM_001184785.2	ENSP00000363920.3		Q8TEW0-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000159

AC:

AN:

251204

AF XY:

0.0000295

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000176

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000198

AC:

AN:

1461806

Hom.:

Cov.:

AF XY:

0.0000261

AC XY:

AN XY:

727202

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33474

American (AMR)

AF:

0.00

AC:

AN:

44710

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26132

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39696

South Asian (SAS)

AF:

0.0000232

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

0.0000234

AC:

AN:

1111958

Other (OTH)

AF:

0.00

AC:

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.444

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

Cov.:

Alfa

AF:

0.0000329

Hom.:

ExAC

AF:

0.0000247

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.96

BayesDel_addAF

Benign

0.0054

BayesDel_noAF

Uncertain

-0.050

CADD

Pathogenic

(source)

DANN

Pathogenic

1.0

DEOGEN2

Uncertain

0.49

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

Eigen

Pathogenic

0.72

Eigen_PC

Pathogenic

0.72

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.97

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

M_CAP

Benign

0.024

MetaRNN

Uncertain

0.48

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

MetaSVM

Benign

-0.97

MutationAssessor

Uncertain

2.7

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

PhyloP100

PrimateAI

Pathogenic

0.91

PROVEAN

Pathogenic

-6.9

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

REVEL

Uncertain

0.40

Sift

Uncertain

0.0010

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

Sift4G

Uncertain

0.012

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

Polyphen

1.0

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

Vest4

0.73

MVP

0.58

MPC

0.45

ClinPred

0.91

GERP RS

5.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.31

gMVP

0.37

Mutation Taster

=89/11

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over