rs942431

Positions:

• chr10-34683859-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001184785.2(PARD3):​c.222+12459A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.298 in 152,068 control chromosomes in the GnomAD database, including 6,866 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.30 (6866 hom., cov: 30)
• Consequence: PARD3 NM_001184785.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.80

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.36 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PARD3	NM_001184785.2	c.222+12459A>G		intron_variant		ENST00000374788.8	NP_001171714.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PARD3	ENST00000374788.8	c.222+12459A>G		intron_variant		1	NM_001184785.2	ENSP00000363920	A1

Frequencies

GnomAD3 genomes AF: 0.298 AC: 45284 AN: 151950 Hom.: 6858 Cov.: 30

Gnomad AFR AF: 0.255

Gnomad AMI AF: 0.314

Gnomad AMR AF: 0.335

Gnomad ASJ AF: 0.316

Gnomad EAS AF: 0.343

Gnomad SAS AF: 0.375

Gnomad FIN AF: 0.385

Gnomad MID AF: 0.294

Gnomad NFE AF: 0.293

Gnomad OTH AF: 0.275

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.298 AC: 45322 AN: 152068 Hom.: 6866 Cov.: 30 AF XY: 0.303 AC XY: 22533 AN XY: 74312

Gnomad4 AFR AF: 0.255

Gnomad4 AMR AF: 0.336

Gnomad4 ASJ AF: 0.316

Gnomad4 EAS AF: 0.343

Gnomad4 SAS AF: 0.375

Gnomad4 FIN AF: 0.385

Gnomad4 NFE AF: 0.293

Gnomad4 OTH AF: 0.279

Alfa AF: 0.309 Hom.: 913

Bravo AF: 0.292

Asia WGS AF: 0.395 AC: 1373 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.011
DANN	Benign	0.74

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

Other links and lift over

dbSNP: rs942431; hg19: chr10-34972787;