rs765823995

Variant names:

• chr2-204546054-G-A
• rs765823995
• NM_001302769.2:c.55G>A

Variant summary

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

The NM_001302769.2(PARD3B):​c.55G>A​(p.Gly19Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000652 in 1,564,972 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000072 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000064 (0 hom.)
• Consequence: PARD3B NM_001302769.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.87
• Publications: 0 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 2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001302769.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PARD3B	NM_001302769.2	MANE Select	c.55G>A	p.Gly19Ser	missense	Exon 1 of 23	NP_001289698.1	Q8TEW8-1
	PARD3B	NM_152526.6		c.55G>A	p.Gly19Ser	missense	Exon 1 of 22	NP_689739.4
	PARD3B	NM_057177.7		c.55G>A	p.Gly19Ser	missense	Exon 1 of 22	NP_476518.4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PARD3B	ENST00000406610.7	TSL:1 MANE Select	c.55G>A	p.Gly19Ser	missense	Exon 1 of 23	ENSP00000385848.2	Q8TEW8-1
	PARD3B	ENST00000358768.6	TSL:1	c.55G>A	p.Gly19Ser	missense	Exon 1 of 22	ENSP00000351618.2	Q8TEW8-2
	PARD3B	ENST00000351153.5	TSL:1	c.55G>A	p.Gly19Ser	missense	Exon 1 of 22	ENSP00000317261.2	Q8TEW8-6

Frequencies

GnomAD3 genomes AF: 0.0000723 AC: 11 AN: 152186 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000424 AC: 7 AN: 165188 AF XY: 0.0000448

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000357

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000945

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000644 AC: 91 AN: 1412786 Hom.: 0 Cov.: 31 AF XY: 0.0000687 AC XY: 48 AN XY: 698470

African (AFR) AF: 0.0000312 AC: 1 AN: 32058

American (AMR) AF: 0.0000254 AC: 1 AN: 39382

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25332

East Asian (EAS) AF: 0.00 AC: 0 AN: 36556

South Asian (SAS) AF: 0.00 AC: 0 AN: 80624

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48658

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5714

European-Non Finnish (NFE) AF: 0.0000810 AC: 88 AN: 1086058

Other (OTH) AF: 0.0000171 AC: 1 AN: 58404

GnomAD4 genome AF: 0.0000723 AC: 11 AN: 152186 Hom.: 0 Cov.: 32 AF XY: 0.0000404 AC XY: 3 AN XY: 74342

African (AFR) AF: 0.00 AC: 0 AN: 41454

American (AMR) AF: 0.0000654 AC: 1 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5162

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000147 AC: 10 AN: 68034

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.0000838 Hom.: 0

Bravo AF: 0.0000529

TwinsUK AF: 0.000539 AC: 2

ALSPAC AF: 0.00 AC: 0

ExAC AF: 0.0000346 AC: 4

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.43
BayesDel_addAF	Uncertain	0.095	D
BayesDel_noAF	Uncertain	0.10
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.044	T
Eigen	Pathogenic	0.69
Eigen_PC	Pathogenic	0.67
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.83	T
M_CAP	Uncertain	0.18	D
MetaRNN	Uncertain	0.63	D
MetaSVM	Benign	-0.62	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		6.9
PrimateAI	Pathogenic	0.84	D
PROVEAN	Uncertain	-3.4	D
REVEL	Uncertain	0.42
Sift	Uncertain	0.0020	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.83
MVP		0.72
MPC		0.19
ClinPred		0.78	D
GERP RS		5.1
PromoterAI		-0.081	Neutral
Varity_R		0.72
gMVP		0.49
Mutation Taster		=63/37	polymorphism

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

Other links and lift over

dbSNP: rs765823995; hg19: chr2-205410777;