rs1114167354

chr10-34341696-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP5

The NM_001184785.2(PARD3):c.2339A>G(p.Asp780Gly) 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).

• Frequency: Genomes: not found (cov: 32)
• Consequence: PARD3 NM_001184785.2 missense
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 7.67

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 10-34341696-T-C is Pathogenic according to our data. Variant chr10-34341696-T-C is described in ClinVar as [Pathogenic]. Clinvar id is 254187.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.2339A>G	p.Asp780Gly	missense_variant	16/25	ENST00000374788.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PARD3	ENST00000374788.8	c.2339A>G	p.Asp780Gly	missense_variant	16/25	1	NM_001184785.2	A1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

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	0.75
BayesDel_addAF	Uncertain	0.097	D
BayesDel_noAF	Benign	-0.10
Cadd	Uncertain	25
Dann	Uncertain	1.0
Eigen	Uncertain	0.58
Eigen_PC	Uncertain	0.58
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Pathogenic	1.0	D;D;D;D;D;D;D;D;D;D;D;D
M_CAP	Benign	0.043	D
MetaRNN	Uncertain	0.63	D;D;D;D;D;D;D;D;D;D;D;D
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	1.0	D;D;D;D;D;D;D;D;D;D;D;D
PrimateAI	Uncertain	0.68	T
PROVEAN	Pathogenic	-5.1	D;D;D;D;D;D;D;D;D;D;D;D
REVEL	Benign	0.27
Sift	Uncertain	0.0040	D;D;D;D;D;D;D;D;D;D;D;D
Sift4G	Uncertain	0.040	D;D;T;D;T;D;D;D;D;D;D;D
Polyphen		1.0	D;.;B;D;D;D;D;P;D;D;D;D
Vest4		0.77
MutPred		0.23		.;.;Loss of stability (P = 0.0086);.;Loss of stability (P = 0.0086);.;.;.;.;.;.;.;
MVP		0.61
MPC		0.49
ClinPred		1.0	D
GERP RS		5.6
Varity_R		0.54
gMVP		0.50

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: rs1114167354; hg19: chr10-34630624;