10-34382893-C-A

Variant names:

• chr10-34382893-C-A
• rs199923448
• NM_001184785.2:c.1046G>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001184785.2(PARD3):​c.1046G>T​(p.Arg349Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000197 in 152,176 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R349H) has been classified as Uncertain significance.

• Frequency: Genomes: 𝑓 0.000020 (0 hom., cov: 32)
• Consequence: PARD3 NM_001184785.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.33
• Publications: 5 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.1046G>T	p.Arg349Leu	missense	Exon 9 of 25	NP_001171714.1	Q8TEW0-2
	PARD3	NM_019619.4		c.1046G>T	p.Arg349Leu	missense	Exon 9 of 25	NP_062565.2
	PARD3	NM_001184786.2		c.1046G>T	p.Arg349Leu	missense	Exon 9 of 24	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.1046G>T	p.Arg349Leu	missense	Exon 9 of 25	ENSP00000363920.3	Q8TEW0-2
	PARD3	ENST00000374789.8	TSL:1	c.1046G>T	p.Arg349Leu	missense	Exon 9 of 25	ENSP00000363921.3	Q8TEW0-1
	PARD3	ENST00000545693.5	TSL:1	c.1046G>T	p.Arg349Leu	missense	Exon 9 of 24	ENSP00000443147.1	Q8TEW0-11

Frequencies

GnomAD3 genomes AF: 0.0000197 AC: 3 AN: 152058 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000242

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000415

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000796 AC: 2 AN: 251288 AF XY: 0.00000736

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 32

GnomAD4 genome AF: 0.0000197 AC: 3 AN: 152176 Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1 AN XY: 74398

African (AFR) AF: 0.0000241 AC: 1 AN: 41514

American (AMR) AF: 0.00 AC: 0 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.000416 AC: 2 AN: 4812

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10578

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68018

Other (OTH) AF: 0.00 AC: 0 AN: 2112

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ExAC AF: 0.0000165 AC: 2

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.42
BayesDel_addAF	Uncertain	0.14	D
BayesDel_noAF	Pathogenic	0.14
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.48	T
Eigen	Uncertain	0.54
Eigen_PC	Uncertain	0.62
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Pathogenic	0.98	D
M_CAP	Uncertain	0.092	D
MetaRNN	Uncertain	0.66	D
MetaSVM	Uncertain	0.33	D
MutationAssessor	Uncertain	2.2	M
PhyloP100		7.3
PrimateAI	Uncertain	0.69	T
PROVEAN	Pathogenic	-5.2	D
REVEL	Pathogenic	0.70
Sift	Uncertain	0.0090	D
Sift4G	Uncertain	0.026	D
Polyphen		0.20	B
Vest4		0.77
MutPred		0.56		Loss of MoRF binding (P = 6e-04)
MVP		0.83
MPC		0.57
ClinPred		0.77	D
GERP RS		5.7
Varity_R		0.57
gMVP		0.71
Mutation Taster		=38/62	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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: rs199923448; hg19: chr10-34671821;