rs2384137

Positions:

• chr10-34323557-A-G
• chr10-34323557-A-T

Variant summary

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

The ENST00000374788.8(PARD3):​c.2834-6219T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0551 in 152,258 control chromosomes in the GnomAD database, including 421 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 0.055 (421 hom., cov: 32)
• Consequence: PARD3 ENST00000374788.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.08

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=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.126 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PARD3	NM_001184785.2	c.2834-6219T>C		intron_variant		ENST00000374788.8	NP_001171714.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PARD3	ENST00000374788.8	c.2834-6219T>C		intron_variant		1	NM_001184785.2	ENSP00000363920	A1

Frequencies

GnomAD3 genomes AF: 0.0551 AC: 8384 AN: 152140 Hom.: 419 Cov.: 32

Gnomad AFR AF: 0.129

Gnomad AMI AF: 0.0197

Gnomad AMR AF: 0.0228

Gnomad ASJ AF: 0.0147

Gnomad EAS AF: 0.0585

Gnomad SAS AF: 0.0391

Gnomad FIN AF: 0.0568

Gnomad MID AF: 0.0191

Gnomad NFE AF: 0.0212

Gnomad OTH AF: 0.0344

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

GnomAD4 genome AF: 0.0551 AC: 8393 AN: 152258 Hom.: 421 Cov.: 32 AF XY: 0.0550 AC XY: 4092 AN XY: 74456

Gnomad4 AFR AF: 0.129

Gnomad4 AMR AF: 0.0228

Gnomad4 ASJ AF: 0.0147

Gnomad4 EAS AF: 0.0579

Gnomad4 SAS AF: 0.0390

Gnomad4 FIN AF: 0.0568

Gnomad4 NFE AF: 0.0212

Gnomad4 OTH AF: 0.0346

Alfa AF: 0.0171 Hom.: 18

Bravo AF: 0.0555

Asia WGS AF: 0.0610 AC: 211 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.60
DANN	Benign	0.81

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: rs2384137; hg19: chr10-34612485;