rs493392

Positions:

• chr10-34542959-G-C

Variant summary

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

The NM_001184785.2(PARD3):​c.223-25800C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.481 in 152,012 control chromosomes in the GnomAD database, including 18,375 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 0.48 (18375 hom., cov: 33)
• Consequence: PARD3 NM_001184785.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.264

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=-1.02).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.636 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PARD3	NM_001184785.2	c.223-25800C>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.223-25800C>G		intron_variant		1	NM_001184785.2	ENSP00000363920	A1

Frequencies

GnomAD3 genomes AF: 0.481 AC: 73031 AN: 151894 Hom.: 18343 Cov.: 33

Gnomad AFR AF: 0.642

Gnomad AMI AF: 0.394

Gnomad AMR AF: 0.431

Gnomad ASJ AF: 0.371

Gnomad EAS AF: 0.420

Gnomad SAS AF: 0.453

Gnomad FIN AF: 0.486

Gnomad MID AF: 0.420

Gnomad NFE AF: 0.408

Gnomad OTH AF: 0.451

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

GnomAD4 genome AF: 0.481 AC: 73117 AN: 152012 Hom.: 18375 Cov.: 33 AF XY: 0.483 AC XY: 35889 AN XY: 74306

Gnomad4 AFR AF: 0.642

Gnomad4 AMR AF: 0.431

Gnomad4 ASJ AF: 0.371

Gnomad4 EAS AF: 0.419

Gnomad4 SAS AF: 0.452

Gnomad4 FIN AF: 0.486

Gnomad4 NFE AF: 0.408

Gnomad4 OTH AF: 0.453

Alfa AF: 0.465 Hom.: 2106

Bravo AF: 0.484

Asia WGS AF: 0.483 AC: 1678 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.75
DANN	Benign	0.40

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: rs493392; hg19: chr10-34831887;