NM_001184785.2:c.3420-21825A>G

Variant names:

• chr10-34153408-T-C
• rs673009
• NM_001184785.2:c.3420-21825A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_001184785.2(PARD3):​c.3420-21825A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0259 in 152,316 control chromosomes in the GnomAD database, including 92 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 0.026 (92 hom., cov: 33)
• Consequence: PARD3 NM_001184785.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.75
• Publications: 1 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0259 (3949/152316) while in subpopulation NFE AF = 0.0372 (2531/68028). AF 95% confidence interval is 0.036. There are 92 homozygotes in GnomAd4. There are 1858 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High AC in GnomAd4 at 3949 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001184785.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PARD3	NM_001184785.2	MANE Select	c.3420-21825A>G		intron	N/A	NP_001171714.1	Q8TEW0-2
	PARD3	NM_019619.4		c.3429-21825A>G		intron	N/A	NP_062565.2
	PARD3	NM_001184786.2		c.3381-21825A>G		intron	N/A	NP_001171715.1	Q8TEW0-11

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PARD3	ENST00000374788.8	TSL:1 MANE Select	c.3420-21825A>G		intron	N/A	ENSP00000363920.3	Q8TEW0-2
	PARD3	ENST00000374789.8	TSL:1	c.3429-21825A>G		intron	N/A	ENSP00000363921.3	Q8TEW0-1
	PARD3	ENST00000545693.5	TSL:1	c.3381-21825A>G		intron	N/A	ENSP00000443147.1	Q8TEW0-11

Frequencies

GnomAD3 genomes AF: 0.0260 AC: 3950 AN: 152198 Hom.: 92 Cov.: 33

Gnomad AFR AF: 0.00909

Gnomad AMI AF: 0.0559

Gnomad AMR AF: 0.0282

Gnomad ASJ AF: 0.0251

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00415

Gnomad FIN AF: 0.0362

Gnomad MID AF: 0.0191

Gnomad NFE AF: 0.0372

Gnomad OTH AF: 0.0301

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

GnomAD4 genome AF: 0.0259 AC: 3949 AN: 152316 Hom.: 92 Cov.: 33 AF XY: 0.0249 AC XY: 1858 AN XY: 74470

African (AFR) AF: 0.00907 AC: 377 AN: 41582

American (AMR) AF: 0.0282 AC: 431 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0251 AC: 87 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00415 AC: 20 AN: 4816

European-Finnish (FIN) AF: 0.0362 AC: 384 AN: 10606

Middle Eastern (MID) AF: 0.0171 AC: 5 AN: 292

European-Non Finnish (NFE) AF: 0.0372 AC: 2531 AN: 68028

Other (OTH) AF: 0.0298 AC: 63 AN: 2116

Alfa AF: 0.0106 Hom.: 1

Bravo AF: 0.0252

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.035
DANN	Benign	0.65
PhyloP100		-2.7
Mutation Taster		=100/0	polymorphism

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: rs673009; hg19: chr10-34442336;