10-34331292-C-T

Variant names:

• chr10-34331292-C-T
• rs3781128
• NM_001184785.2:c.2658G>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6 BP7 BA1

The NM_001184785.2(PARD3):​c.2658G>A​(p.Ser886Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.483 in 1,612,910 control chromosomes in the GnomAD database, including 191,218 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.54 (22893 hom., cov: 31)
  • Exomes 𝑓: 0.48 (168325 hom.)
• Consequence: PARD3 NM_001184785.2 synonymous
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: -3.84
• Publications: 31 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.71).
• BP6: Variant 10-34331292-C-T is Benign according to our data. Variant chr10-34331292-C-T is described in ClinVar as Benign. ClinVar VariationId is 3060980.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=-3.84 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.695 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PARD3	NM_001184785.2	c.2658G>A	p.Ser886Ser	synonymous_variant	Exon 19 of 25	ENST00000374788.8	NP_001171714.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PARD3	ENST00000374788.8	c.2658G>A	p.Ser886Ser	synonymous_variant	Exon 19 of 25	1	NM_001184785.2	ENSP00000363920.3

Frequencies

GnomAD3 genomes AF: 0.537 AC: 81542 AN: 151722 Hom.: 22842 Cov.: 31

Gnomad AFR AF: 0.701

Gnomad AMI AF: 0.407

Gnomad AMR AF: 0.515

Gnomad ASJ AF: 0.530

Gnomad EAS AF: 0.374

Gnomad SAS AF: 0.540

Gnomad FIN AF: 0.482

Gnomad MID AF: 0.471

Gnomad NFE AF: 0.466

Gnomad OTH AF: 0.527

GnomAD2 exomes AF: 0.490 AC: 122927 AN: 251086 AF XY: 0.488

Gnomad AFR exome AF: 0.708

Gnomad AMR exome AF: 0.480

Gnomad ASJ exome AF: 0.517

Gnomad EAS exome AF: 0.373

Gnomad FIN exome AF: 0.482

Gnomad NFE exome AF: 0.469

Gnomad OTH exome AF: 0.493

GnomAD4 exome AF: 0.478 AC: 697921 AN: 1461068 Hom.: 168325 Cov.: 40 AF XY: 0.478 AC XY: 347568 AN XY: 726842

African (AFR) AF: 0.710 AC: 23744 AN: 33452

American (AMR) AF: 0.483 AC: 21588 AN: 44708

Ashkenazi Jewish (ASJ) AF: 0.515 AC: 13460 AN: 26128

East Asian (EAS) AF: 0.397 AC: 15751 AN: 39690

South Asian (SAS) AF: 0.523 AC: 45113 AN: 86250

European-Finnish (FIN) AF: 0.479 AC: 25554 AN: 53404

Middle Eastern (MID) AF: 0.466 AC: 2683 AN: 5762

European-Non Finnish (NFE) AF: 0.468 AC: 520354 AN: 1111328

Other (OTH) AF: 0.492 AC: 29674 AN: 60346

GnomAD4 genome AF: 0.538 AC: 81655 AN: 151842 Hom.: 22893 Cov.: 31 AF XY: 0.539 AC XY: 40009 AN XY: 74172

African (AFR) AF: 0.701 AC: 29061 AN: 41430

American (AMR) AF: 0.515 AC: 7858 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.530 AC: 1834 AN: 3462

East Asian (EAS) AF: 0.374 AC: 1922 AN: 5136

South Asian (SAS) AF: 0.539 AC: 2596 AN: 4812

European-Finnish (FIN) AF: 0.482 AC: 5075 AN: 10520

Middle Eastern (MID) AF: 0.486 AC: 142 AN: 292

European-Non Finnish (NFE) AF: 0.466 AC: 31682 AN: 67920

Other (OTH) AF: 0.528 AC: 1115 AN: 2110

Alfa AF: 0.490 Hom.: 64470

Bravo AF: 0.548

Asia WGS AF: 0.480 AC: 1672 AN: 3478

EpiCase AF: 0.477

EpiControl AF: 0.473

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

PARD3-related disorder Benign:1

Oct 17, 2019

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	-0.71
CADD	Benign	0.58
DANN	Benign	0.75
PhyloP100		-3.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=99/1	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3781128; hg19: chr10-34620220; COSMIC: COSV60750250;