NM_001184785.2:c.2729C>A

Variant names:

• chr10-34331221-G-T
• rs781461462
• NM_001184785.2:c.2729C>A

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP5

The NM_001184785.2(PARD3):​c.2729C>A​(p.Pro910Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars). Synonymous variant affecting the same amino acid position (i.e. P910P) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PARD3 NM_001184785.2 missense
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 10.0
• Publications: 2 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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 10-34331221-G-T is Pathogenic according to our data. Variant chr10-34331221-G-T is described in ClinVar as Pathogenic. ClinVar VariationId is 254185.Status of the report is no_assertion_criteria_provided, 0 stars.

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.2729C>A	p.Pro910Gln	missense	Exon 19 of 25	NP_001171714.1	Q8TEW0-2
	PARD3	NM_019619.4		c.2738C>A	p.Pro913Gln	missense	Exon 19 of 25	NP_062565.2
	PARD3	NM_001184786.2		c.2690C>A	p.Pro897Gln	missense	Exon 18 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.2729C>A	p.Pro910Gln	missense	Exon 19 of 25	ENSP00000363920.3	Q8TEW0-2
	PARD3	ENST00000374789.8	TSL:1	c.2738C>A	p.Pro913Gln	missense	Exon 19 of 25	ENSP00000363921.3	Q8TEW0-1
	PARD3	ENST00000545693.5	TSL:1	c.2690C>A	p.Pro897Gln	missense	Exon 18 of 24	ENSP00000443147.1	Q8TEW0-11

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Pathogenic

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
1	-	-	Neural tube defect (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.96
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.070
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.49	T
Eigen	Pathogenic	0.75
Eigen_PC	Pathogenic	0.74
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.95	D
M_CAP	Benign	0.017	T
MetaRNN	Uncertain	0.46	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		10
PrimateAI	Pathogenic	0.88	D
PROVEAN	Pathogenic	-5.3	D
REVEL	Uncertain	0.45
Sift	Benign	0.040	D
Sift4G	Benign	0.17	T
Polyphen		1.0	D
Vest4		0.60
MutPred		0.35		Loss of sheet (P = 0.0228)
MVP		0.57
MPC		0.44
ClinPred		0.99	D
GERP RS		5.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.33
gMVP		0.38
Mutation Taster		=1/99	disease causing (ClinVar)

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: rs781461462; hg19: chr10-34620149;