Genetic Variant NM_001184785.2:c.*4C>T (chr10-34111165-G-A) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2

The NM_001184785.2(PARD3):c.*4C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0205 in 1,534,906 control chromosomes in the GnomAD database, including 399 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.016 ( 25 hom., cov: 32)

Exomes 𝑓: 0.021 ( 374 hom. )

Consequence

PARD3
NM_001184785.2 3_prime_UTR

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.0280

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: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 10-34111165-G-A is Benign according to our data. Variant chr10-34111165-G-A is described in ClinVar as [Benign]. Clinvar id is 3056597.Status of the report is no_assertion_criteria_provided, 0 stars.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0159 (2418/152284) while in subpopulation NFE AF = 0.0235 (1601/68030). AF 95% confidence interval is 0.0226. There are 25 homozygotes in GnomAd4. There are 1191 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High AC in GnomAd4 at 2418 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PARD3	NM_001184785.2 link	c.*4C>T		3_prime_UTR_variant	Exon 25 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.*4C>T		3_prime_UTR_variant	Exon 25 of 25	1	NM_001184785.2	ENSP00000363920.3		Q8TEW0-2

Frequencies

GnomAD3 genomes

AF:

0.0159

AC:

2418

AN:

152166

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00401

Gnomad AMI

AF:

0.0121

Gnomad AMR

AF:

0.0184

Gnomad ASJ

AF:

0.00490

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00807

Gnomad FIN

AF:

0.0243

Gnomad MID

AF:

0.0316

Gnomad NFE

AF:

0.0235

Gnomad OTH

AF:

0.0163

GnomAD2 exomes

AF:

0.0168

AC:

3384

AN:

201472

AF XY:

0.0172

show subpopulations

Gnomad AFR exome

AF:

0.00370

Gnomad AMR exome

AF:

0.0102

Gnomad ASJ exome

AF:

0.00892

Gnomad EAS exome

AF:

0.000185

Gnomad FIN exome

AF:

0.0255

Gnomad NFE exome

AF:

0.0240

Gnomad OTH exome

AF:

0.0181

GnomAD4 exome

AF:

0.0210

AC:

29065

AN:

1382622

Hom.:

374

Cov.:

AF XY:

0.0208

AC XY:

14120

AN XY:

678958

show subpopulations

African (AFR)

AF:

0.00293

AC:

AN:

30416

American (AMR)

AF:

0.0100

AC:

310

AN:

30882

Ashkenazi Jewish (ASJ)

AF:

0.00690

AC:

151

AN:

21878

East Asian (EAS)

AF:

0.000104

AC:

AN:

38630

South Asian (SAS)

AF:

0.00711

AC:

531

AN:

74726

European-Finnish (FIN)

AF:

0.0246

AC:

1259

AN:

51084

Middle Eastern (MID)

AF:

0.00723

AC:

AN:

5392

European-Non Finnish (NFE)

AF:

0.0240

AC:

25778

AN:

1072874

Other (OTH)

AF:

0.0159

AC:

904

AN:

56740

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.471

Heterozygous variant carriers

1319

2638

3958

5277

6596

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0159

AC:

2418

AN:

152284

Hom.:

Cov.:

AF XY:

0.0160

AC XY:

1191

AN XY:

74460

show subpopulations

African (AFR)

AF:

0.00399

AC:

166

AN:

41556

American (AMR)

AF:

0.0184

AC:

281

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.00490

AC:

AN:

3468

East Asian (EAS)

AF:

0.000193

AC:

AN:

5188

South Asian (SAS)

AF:

0.00829

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.0243

AC:

258

AN:

10600

Middle Eastern (MID)

AF:

0.0306

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0235

AC:

1601

AN:

68030

Other (OTH)

AF:

0.0161

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

120

241

361

482

602

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0163

Hom.:

Bravo

AF:

0.0145

Asia WGS

AF:

0.00520

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

PARD3-related disorder

Benign:1

Jan 20, 2020

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

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

BayesDel_noAF

Benign

-0.83

CADD

Benign

1.5

(source)

DANN

Benign

0.76

PhyloP100

0.028

Mutation Taster

=100/0

polymorphism (auto)

(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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NM_001184785.2:c.*4C>T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over