NM_001184785.2:c.572G>T

Variant names:

• chr10-34470095-C-A
• rs193920777
• NM_001184785.2:c.572G>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001184785.2(PARD3):​c.572G>T​(p.Cys191Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. C191W) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PARD3 NM_001184785.2 missense
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 3.09
• Publications: 0 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.11762911).

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.572G>T	p.Cys191Phe	missense	Exon 4 of 25	NP_001171714.1
	PARD3	NM_019619.4		c.572G>T	p.Cys191Phe	missense	Exon 4 of 25	NP_062565.2
	PARD3	NM_001184786.2		c.572G>T	p.Cys191Phe	missense	Exon 4 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.572G>T	p.Cys191Phe	missense	Exon 4 of 25	ENSP00000363920.3
	PARD3	ENST00000374789.8	TSL:1	c.572G>T	p.Cys191Phe	missense	Exon 4 of 25	ENSP00000363921.3
	PARD3	ENST00000545693.5	TSL:1	c.572G>T	p.Cys191Phe	missense	Exon 4 of 24	ENSP00000443147.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	1	-	Prostate cancer (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.087
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	23
DANN	Benign	0.96
DEOGEN2	Benign	0.22	T
Eigen	Benign	-0.19
Eigen_PC	Benign	-0.0064
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Uncertain	0.95	D
M_CAP	Benign	0.0092	T
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.1	L
PhyloP100		3.1
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-2.2	N
REVEL	Benign	0.10
Sift	Benign	0.069	T
Sift4G	Benign	0.57	T
Polyphen		0.43	B
Vest4		0.37
MutPred		0.13		Gain of MoRF binding (P = 0.0775)
MVP		0.27
MPC		0.67
ClinPred		0.78	D
GERP RS		5.0
Varity_R		0.25
gMVP		0.21
Mutation Taster		=88/12	polymorphism

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: rs193920777; hg19: chr10-34759023; COSMIC: COSV60765296;