rs188923583

Variant names:

• chr2-204686210-C-T
• rs188923583
• NM_001302769.2:c.150C>T

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_Moderate BP6_Moderate BP7

The NM_001302769.2(PARD3B):​c.150C>T​(p.His50His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000259 in 1,612,218 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 Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0014 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00014 (0 hom.)
• Consequence: PARD3B NM_001302769.2 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.03
• 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: Likely_benign. The variant received -5 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.4).
• BP6: Variant 2-204686210-C-T is Benign according to our data. Variant chr2-204686210-C-T is described in ClinVar as Benign. ClinVar VariationId is 783350.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=1.03 with no splicing effect.

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.150C>T	p.His50His	synonymous	Exon 2 of 23	NP_001289698.1	Q8TEW8-1
	PARD3B	NM_152526.6		c.150C>T	p.His50His	synonymous	Exon 2 of 22	NP_689739.4
	PARD3B	NM_057177.7		c.150C>T	p.His50His	synonymous	Exon 2 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.150C>T	p.His50His	synonymous	Exon 2 of 23	ENSP00000385848.2	Q8TEW8-1
	PARD3B	ENST00000358768.6	TSL:1	c.150C>T	p.His50His	synonymous	Exon 2 of 22	ENSP00000351618.2	Q8TEW8-2
	PARD3B	ENST00000351153.5	TSL:1	c.150C>T	p.His50His	synonymous	Exon 2 of 22	ENSP00000317261.2	Q8TEW8-6

Frequencies

GnomAD3 genomes AF: 0.00143 AC: 218 AN: 152130 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00480

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000721

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00287

GnomAD2 exomes AF: 0.000421 AC: 105 AN: 249122 AF XY: 0.000274

Gnomad AFR exome AF: 0.00601

Gnomad AMR exome AF: 0.000232

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: 0.000331

GnomAD4 exome AF: 0.000137 AC: 200 AN: 1459970 Hom.: 0 Cov.: 29 AF XY: 0.000117 AC XY: 85 AN XY: 726358

African (AFR) AF: 0.00446 AC: 149 AN: 33396

American (AMR) AF: 0.000492 AC: 22 AN: 44674

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26100

East Asian (EAS) AF: 0.00 AC: 0 AN: 39620

South Asian (SAS) AF: 0.0000464 AC: 4 AN: 86224

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53406

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5758

European-Non Finnish (NFE) AF: 0.00000360 AC: 4 AN: 1110466

Other (OTH) AF: 0.000348 AC: 21 AN: 60326

GnomAD4 genome AF: 0.00143 AC: 217 AN: 152248 Hom.: 0 Cov.: 32 AF XY: 0.00140 AC XY: 104 AN XY: 74442

African (AFR) AF: 0.00476 AC: 198 AN: 41566

American (AMR) AF: 0.000720 AC: 11 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5172

South Asian (SAS) AF: 0.000414 AC: 2 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10614

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67998

Other (OTH) AF: 0.00284 AC: 6 AN: 2112

Alfa AF: 0.00105 Hom.: 0

Bravo AF: 0.00178

Asia WGS AF: 0.000577 AC: 2 AN: 3478

EpiCase AF: 0.00

EpiControl AF: 0.0000593

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.29
BayesDel_noAF	Benign	-0.40
CADD	Benign	7.6
DANN	Benign	0.96
PhyloP100		1.0
Mutation Taster		=100/0	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: rs188923583; hg19: chr2-205550933;