2-205113512-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001302769.2(PARD3B):c.615G>T(p.Glu205Asp) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,198 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: PARD3B NM_001302769.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.10

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3851565).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PARD3B	NM_001302769.2	c.615G>T	p.Glu205Asp	missense_variant	6/23	ENST00000406610.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PARD3B	ENST00000406610.7	c.615G>T	p.Glu205Asp	missense_variant	6/23	1	NM_001302769.2	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000804 AC: 2 AN: 248668 Hom.: 0 AF XY: 0.00000741 AC XY: 1 AN XY: 134948

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000584

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461198 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 726902

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000448

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 08, 2022

The c.615G>T (p.E205D) alteration is located in exon 6 (coding exon 6) of the PARD3B gene. This alteration results from a G to T substitution at nucleotide position 615, causing the glutamic acid (E) at amino acid position 205 to be replaced by an aspartic acid (D). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.077	T
BayesDel_noAF	Benign	-0.35
Cadd	Benign	21
Dann	Uncertain	1.0
DEOGEN2	Benign	0.11	T;T;.;.;.;.;.;T
Eigen	Uncertain	0.60
Eigen_PC	Uncertain	0.56
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.83	T;T;T;T;T;T;T;T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.39	T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.93	T
MutationAssessor	Uncertain	2.5	M;.;M;M;M;.;.;.
MutationTaster	Benign	0.97	D;D;D;D
PrimateAI	Uncertain	0.62	T
PROVEAN	Uncertain	-2.8	D;.;D;D;D;.;.;.
REVEL	Benign	0.16
Sift	Uncertain	0.0050	D;.;D;D;D;.;.;.
Sift4G	Uncertain	0.0050	D;D;D;D;D;D;D;D
Polyphen		1.0	D;.;D;.;D;.;.;.
Vest4		0.23
MutPred		0.29		Loss of glycosylation at S207 (P = 0.1108);Loss of glycosylation at S207 (P = 0.1108);Loss of glycosylation at S207 (P = 0.1108);Loss of glycosylation at S207 (P = 0.1108);Loss of glycosylation at S207 (P = 0.1108);.;.;.;
MVP		0.66
MPC		0.024
ClinPred		0.88	D
GERP RS		4.6
Varity_R		0.58
gMVP		0.52

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: rs775487298; hg19: chr2-205978236;