10-34331221-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 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

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 Uncertain_significance. Variant got 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 id is 254185.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PARD3	NM_001184785.2	c.2729C>A	p.Pro910Gln	missense_variant	19/25	ENST00000374788.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PARD3	ENST00000374788.8	c.2729C>A	p.Pro910Gln	missense_variant	19/25	1	NM_001184785.2	A1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Neural tube defect Pathogenic:1

Pathogenic, no assertion criteria provided

case-control

Beijing Municipal Key Laboratory, Capital Institute of Pediatrics

May 01, 2016

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Computational scores

Source: dbNSFP v4.3

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
Eigen	Pathogenic	0.75
Eigen_PC	Pathogenic	0.74
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.95	D;D;D;D;D;D;D;D;D;D;D;D
M_CAP	Benign	0.017	T
MetaRNN	Uncertain	0.46	T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.91	T
MutationTaster	Benign	1.0	D;D;D;D;D;D;D;D;D;D;D;D
PrimateAI	Pathogenic	0.88	D
PROVEAN	Pathogenic	-5.3	D;D;D;D;D;D;D;D;D;D;D;D
REVEL	Uncertain	0.45
Sift	Benign	0.040	D;T;T;T;T;D;T;D;T;T;T;T
Sift4G	Benign	0.17	T;T;T;T;T;T;T;T;T;T;T;T
Polyphen		1.0	D;.;P;D;P;D;D;D;P;D;P;D
Vest4		0.60
MutPred		0.35		.;.;Loss of sheet (P = 0.0228);.;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

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: rs781461462; hg19: chr10-34620149;