10-34341696-T-C

Variant names:

• chr10-34341696-T-C
• rs1114167354
• NM_001184785.2:c.2339A>G

Variant summary

Our verdict is Uncertain significance. The variant received 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
• Publications: 1 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 10-34341696-T-C is Pathogenic according to our data. Variant chr10-34341696-T-C is described in ClinVar as Pathogenic. ClinVar VariationId is 254187.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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PARD3	NM_001184785.2	MANE Select	c.2339A>G	p.Asp780Gly	missense	Exon 16 of 25	NP_001171714.1
	PARD3	NM_019619.4		c.2348A>G	p.Asp783Gly	missense	Exon 16 of 25	NP_062565.2
	PARD3	NM_001184786.2		c.2300A>G	p.Asp767Gly	missense	Exon 15 of 24	NP_001171715.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PARD3	ENST00000374788.8	TSL:1 MANE Select	c.2339A>G	p.Asp780Gly	missense	Exon 16 of 25	ENSP00000363920.3
	PARD3	ENST00000374789.8	TSL:1	c.2348A>G	p.Asp783Gly	missense	Exon 16 of 25	ENSP00000363921.3
	PARD3	ENST00000545693.5	TSL:1	c.2300A>G	p.Asp767Gly	missense	Exon 15 of 24	ENSP00000443147.1

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

May 01, 2016

Beijing Municipal Key Laboratory, Capital Institute of Pediatrics

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: case-control

Computational scores

Source: dbNSFP v4.9

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
DEOGEN2	Benign	0.40	T
Eigen	Uncertain	0.58
Eigen_PC	Uncertain	0.58
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Pathogenic	1.0	D
M_CAP	Benign	0.043	D
MetaRNN	Uncertain	0.63	D
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		7.7
PrimateAI	Uncertain	0.68	T
PROVEAN	Pathogenic	-5.1	D
REVEL	Benign	0.27
Sift	Uncertain	0.0040	D
Sift4G	Uncertain	0.040	D
Polyphen		1.0	D
Vest4		0.77
MutPred		0.23		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
Mutation Taster		=0/100	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: rs1114167354; hg19: chr10-34630624;