10-34206361-A-G

Variant names:

• chr10-34206361-A-G
• rs678188
• NM_001184785.2:c.3419+63296T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001184785.2(PARD3):​c.3419+63296T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.31 in 152,174 control chromosomes in the GnomAD database, including 8,747 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 0.31 (8747 hom., cov: 33)
• Consequence: PARD3 NM_001184785.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.939
• Publications: 3 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=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.396 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PARD3	NM_001184785.2	MANE Select	c.3419+63296T>C		intron	N/A	NP_001171714.1
	PARD3	NM_019619.4		c.3428+63296T>C		intron	N/A	NP_062565.2
	PARD3	NM_001184786.2		c.3380+63296T>C		intron	N/A	NP_001171715.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PARD3	ENST00000374788.8	TSL:1 MANE Select	c.3419+63296T>C		intron	N/A	ENSP00000363920.3
	PARD3	ENST00000374789.8	TSL:1	c.3428+63296T>C		intron	N/A	ENSP00000363921.3
	PARD3	ENST00000545693.5	TSL:1	c.3380+63296T>C		intron	N/A	ENSP00000443147.1

Frequencies

GnomAD3 genomes AF: 0.310 AC: 47181 AN: 152056 Hom.: 8748 Cov.: 33

Gnomad AFR AF: 0.147

Gnomad AMI AF: 0.432

Gnomad AMR AF: 0.303

Gnomad ASJ AF: 0.295

Gnomad EAS AF: 0.0878

Gnomad SAS AF: 0.190

Gnomad FIN AF: 0.544

Gnomad MID AF: 0.247

Gnomad NFE AF: 0.400

Gnomad OTH AF: 0.308

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

GnomAD4 genome AF: 0.310 AC: 47180 AN: 152174 Hom.: 8747 Cov.: 33 AF XY: 0.312 AC XY: 23194 AN XY: 74408

African (AFR) AF: 0.147 AC: 6109 AN: 41522

American (AMR) AF: 0.303 AC: 4633 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.295 AC: 1025 AN: 3472

East Asian (EAS) AF: 0.0877 AC: 453 AN: 5168

South Asian (SAS) AF: 0.192 AC: 926 AN: 4832

European-Finnish (FIN) AF: 0.544 AC: 5758 AN: 10590

Middle Eastern (MID) AF: 0.245 AC: 72 AN: 294

European-Non Finnish (NFE) AF: 0.400 AC: 27167 AN: 67974

Other (OTH) AF: 0.304 AC: 643 AN: 2116

Alfa AF: 0.361 Hom.: 18071

Bravo AF: 0.285

Asia WGS AF: 0.141 AC: 492 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.20
DANN	Benign	0.15
PhyloP100		-0.94
Mutation Taster		=100/0	polymorphism (auto)

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: rs678188; hg19: chr10-34495289; COSMIC: COSV61069650; COSMIC: COSV61069650;