rs1753586

Positions:

• chr10-34133269-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.3420-1686A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.492 in 151,926 control chromosomes in the GnomAD database, including 19,796 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 0.49 (19796 hom., cov: 31)
• Consequence: PARD3 NM_001184785.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.283

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=-0.96).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.592 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PARD3	NM_001184785.2	c.3420-1686A>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.3420-1686A>G		intron_variant		1	NM_001184785.2	ENSP00000363920	A1

Frequencies

GnomAD3 genomes AF: 0.493 AC: 74769 AN: 151808 Hom.: 19797 Cov.: 31

Gnomad AFR AF: 0.362

Gnomad AMI AF: 0.627

Gnomad AMR AF: 0.409

Gnomad ASJ AF: 0.651

Gnomad EAS AF: 0.129

Gnomad SAS AF: 0.367

Gnomad FIN AF: 0.622

Gnomad MID AF: 0.554

Gnomad NFE AF: 0.597

Gnomad OTH AF: 0.501

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

GnomAD4 genome AF: 0.492 AC: 74794 AN: 151926 Hom.: 19796 Cov.: 31 AF XY: 0.486 AC XY: 36060 AN XY: 74246

Gnomad4 AFR AF: 0.361

Gnomad4 AMR AF: 0.408

Gnomad4 ASJ AF: 0.651

Gnomad4 EAS AF: 0.129

Gnomad4 SAS AF: 0.368

Gnomad4 FIN AF: 0.622

Gnomad4 NFE AF: 0.597

Gnomad4 OTH AF: 0.497

Alfa AF: 0.549 Hom.: 2923

Bravo AF: 0.473

Asia WGS AF: 0.236 AC: 825 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	1.9
DANN	Benign	0.25

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: rs1753586; hg19: chr10-34422197;