chr2-205104433-C-G

Variant names:

• chr2-205104433-C-G
• rs374453548
• NM_001302769.2:c.512C>G

Variant summary

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

The NM_001302769.2(PARD3B):​c.512C>G​(p.Thr171Arg) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T171M) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: PARD3B NM_001302769.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.32
• Publications: 2 publications found

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

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=0.07097328).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PARD3B	NM_001302769.2	c.512C>G	p.Thr171Arg	missense_variant	Exon 5 of 23	ENST00000406610.7	NP_001289698.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PARD3B	ENST00000406610.7	c.512C>G	p.Thr171Arg	missense_variant	Exon 5 of 23	1	NM_001302769.2	ENSP00000385848.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000402 AC: 1 AN: 249030 AF XY: 0.00000740

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000885

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 33

ExAC AF: 0.00000828 AC: 1

EpiCase AF: 0.00

EpiControl AF: 0.0000593

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.079
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	16
DANN	Benign	0.91
DEOGEN2	Benign	0.0046	T;T;.;.;.;.;.;T
Eigen	Benign	-0.54
Eigen_PC	Benign	-0.52
FATHMM_MKL	Benign	0.52	D
LIST_S2	Benign	0.84	T;T;T;T;T;T;T;T
M_CAP	Benign	0.0054	T
MetaRNN	Benign	0.071	T;T;T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.3	M;.;M;M;M;.;.;.
PhyloP100		1.3
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-1.8	N;.;N;N;N;.;.;.
REVEL	Benign	0.020
Sift	Benign	0.057	T;.;T;T;T;.;.;.
Sift4G	Benign	0.20	T;T;T;T;T;T;T;T
Polyphen		0.64	P;.;B;.;B;.;.;.
Vest4		0.29
MutPred		0.15		Loss of glycosylation at T171 (P = 0.0781);Loss of glycosylation at T171 (P = 0.0781);Loss of glycosylation at T171 (P = 0.0781);Loss of glycosylation at T171 (P = 0.0781);Loss of glycosylation at T171 (P = 0.0781);.;.;.;
MVP		0.46
MPC		0.048
ClinPred		0.079	T
GERP RS		1.4
Varity_R		0.072
gMVP		0.28
Mutation Taster		=97/3	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs374453548; hg19: chr2-205969157;