chr2-205113505-C-A

Position:

• chr2-205113505-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001302769.2(PARD3B):​c.608C>A​(p.Thr203Lys) 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. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T203A) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PARD3B NM_001302769.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.721

Genes affected

PARD3B (HGNC:14446): (par-3 family cell polarity regulator beta) Predicted to enable phosphatidylinositol binding activity. Predicted to be involved in several processes, including establishment of cell polarity; establishment of centrosome localization; and establishment or maintenance of epithelial cell apical/basal polarity. Located in cell junction. Part of protein-containing complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09601891).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PARD3B	NM_001302769.2	c.608C>A	p.Thr203Lys	missense_variant	6/23	ENST00000406610.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PARD3B	ENST00000406610.7	c.608C>A	p.Thr203Lys	missense_variant	6/23	1	NM_001302769.2	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Revvity Omics, Revvity

Sep 13, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	17
DANN	Benign	0.93
DEOGEN2	Benign	0.017	T;T;.;.;.;.;.;T
Eigen	Benign	-0.43
Eigen_PC	Benign	-0.26
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.84	T;T;T;T;T;T;T;T
M_CAP	Benign	0.0089	T
MetaRNN	Benign	0.096	T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.74	N;.;N;N;N;.;.;.
MutationTaster	Benign	0.93	N;N;N;N
PrimateAI	Uncertain	0.50	T
PROVEAN	Uncertain	-2.5	D;.;D;N;N;.;.;.
REVEL	Benign	0.080
Sift	Benign	1.0	T;.;T;T;T;.;.;.
Sift4G	Benign	0.12	T;T;T;T;T;T;T;T
Polyphen		0.021	B;.;B;.;B;.;.;.
Vest4		0.30
MutPred		0.47		Gain of ubiquitination at T203 (P = 0.0121);Gain of ubiquitination at T203 (P = 0.0121);Gain of ubiquitination at T203 (P = 0.0121);Gain of ubiquitination at T203 (P = 0.0121);Gain of ubiquitination at T203 (P = 0.0121);.;.;.;
MVP		0.32
MPC		0.024
ClinPred		0.78	D
GERP RS		3.7
Varity_R		0.23
gMVP		0.59

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-205978229;