10-34450347-C-T

Variant names:

• chr10-34450347-C-T
• rs193921017
• NM_001184785.2:c.684G>A

Variant summary

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

The NM_019619.4(PARD3):​c.684G>A​(p.Met228Ile) 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 Uncertain significance (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: PARD3 NM_019619.4 missense
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 7.25
• 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_019619.4. 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.684G>A	p.Met228Ile	missense	Exon 5 of 25	NP_001171714.1
	PARD3	NM_019619.4		c.684G>A	p.Met228Ile	missense	Exon 5 of 25	NP_062565.2
	PARD3	NM_001184786.2		c.684G>A	p.Met228Ile	missense	Exon 5 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.684G>A	p.Met228Ile	missense	Exon 5 of 25	ENSP00000363920.3
	PARD3	ENST00000374789.8	TSL:1	c.684G>A	p.Met228Ile	missense	Exon 5 of 25	ENSP00000363921.3
	PARD3	ENST00000545693.5	TSL:1	c.684G>A	p.Met228Ile	missense	Exon 5 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	Uncertain	0.48
BayesDel_addAF	Benign	-0.063	T
BayesDel_noAF	Benign	-0.33
CADD	Uncertain	25
DANN	Benign	0.97
DEOGEN2	Benign	0.14	T
Eigen	Benign	0.0030
Eigen_PC	Benign	0.16
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.031	D
MetaRNN	Uncertain	0.45	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.6	L
PhyloP100		7.3
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.13
Sift	Benign	0.15	T
Sift4G	Benign	0.42	T
Polyphen		0.080	B
Vest4		0.70
MutPred		0.32		Loss of MoRF binding (P = 0.0867)
MVP		0.46
MPC		0.51
ClinPred		0.68	D
GERP RS		5.9
Varity_R		0.28
gMVP		0.60
Mutation Taster		=53/47	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: rs193921017; hg19: chr10-34739275; COSMIC: COSV60760689;