rs193921017

Positions:

• chr10-34450347-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001184785.2(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_001184785.2 missense
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 7.25

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 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PARD3	NM_001184785.2	c.684G>A	p.Met228Ile	missense_variant	5/25	ENST00000374788.8	NP_001171714.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PARD3	ENST00000374788.8	c.684G>A	p.Met228Ile	missense_variant	5/25	1	NM_001184785.2	ENSP00000363920.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

Submissions by phenotype

Malignant tumor of prostate Uncertain:1

Uncertain significance, no assertion criteria provided

literature only

Science for Life laboratory, Karolinska Institutet

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Computational scores

Source: dbNSFP v4.3

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;.;.;.;.;.;T
Eigen	Benign	0.0030
Eigen_PC	Benign	0.16
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.94	D;D;D;D;D;D;D;D
M_CAP	Benign	0.031	D
MetaRNN	Uncertain	0.45	T;T;T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.6	L;L;L;L;L;L;L;.
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	-1.2	N;N;N;N;N;N;N;N
REVEL	Benign	0.13
Sift	Benign	0.15	T;T;T;T;T;T;T;T
Sift4G	Benign	0.42	T;T;T;T;T;T;T;T
Polyphen		0.080, 0.12, 0.0010, 0.20	.;B;B;B;B;B;B;.
Vest4		0.70
MutPred		0.32		Loss of MoRF binding (P = 0.0867);Loss of MoRF binding (P = 0.0867);Loss of MoRF binding (P = 0.0867);Loss of MoRF binding (P = 0.0867);Loss of MoRF binding (P = 0.0867);Loss of MoRF binding (P = 0.0867);Loss of MoRF binding (P = 0.0867);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

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: rs193921017; hg19: chr10-34739275; COSMIC: COSV60760689;