chr2-205047649-G-C

Variant names:

• chr2-205047649-G-C
• rs375051020
• NM_001302769.2:c.463G>C

Variant summary

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

The NM_001302769.2(PARD3B):​c.463G>C​(p.Ala155Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000715 in 1,398,710 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: PARD3B NM_001302769.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.325

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=0.10803932).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PARD3B	NM_001302769.2	c.463G>C	p.Ala155Pro	missense_variant	Exon 4 of 23	ENST00000406610.7	NP_001289698.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PARD3B	ENST00000406610.7	c.463G>C	p.Ala155Pro	missense_variant	Exon 4 of 23	1	NM_001302769.2	ENSP00000385848.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000647 AC: 1 AN: 154494 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 81746

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000914

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: 7.15e-7 AC: 1 AN: 1398710 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 689942

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000280

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.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.081
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	0.87
DANN	Benign	0.84
DEOGEN2	Benign	0.0070	T;T;.;.;.;.;.;T
Eigen	Benign	-0.75
Eigen_PC	Benign	-0.87
FATHMM_MKL	Benign	0.12	N
LIST_S2	Benign	0.64	T;T;T;T;T;T;T;T
M_CAP	Benign	0.0078	T
MetaRNN	Benign	0.11	T;T;T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.1	M;.;M;M;M;.;.;.
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-2.1	N;.;N;N;N;.;.;.
REVEL	Benign	0.066
Sift	Uncertain	0.029	D;.;D;D;D;.;.;.
Sift4G	Benign	0.20	T;T;T;T;T;T;T;T
Polyphen		0.91	P;.;P;.;B;.;.;.
Vest4		0.43
MutPred		0.23		Gain of glycosylation at A155 (P = 0.012);Gain of glycosylation at A155 (P = 0.012);Gain of glycosylation at A155 (P = 0.012);Gain of glycosylation at A155 (P = 0.012);Gain of glycosylation at A155 (P = 0.012);.;.;.;
MVP		0.44
MPC		0.025
ClinPred		0.085	T
GERP RS		0.42
Varity_R		0.17
gMVP		0.31

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs375051020; hg19: chr2-205912372;