NM_001302769.2:c.365T>C

Variant names:

• chr2-204965294-T-C
• rs74648966
• NM_001302769.2:c.365T>C

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Strong BP6 BS2

The NM_001302769.2(PARD3B):​c.365T>C​(p.Ile122Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00239 in 1,613,822 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.0020 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0024 (9 hom.)
• Consequence: PARD3B NM_001302769.2 missense
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: 5.50
• Publications: 8 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: Benign. The variant received -9 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.010485053).
• BP6: Variant 2-204965294-T-C is Benign according to our data. Variant chr2-204965294-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 3042161.Status of the report is no_assertion_criteria_provided, 0 stars.
• BS2: High Homozygotes in GnomAdExome4 at 9 AR gene

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.365T>C	p.Ile122Thr	missense	Exon 3 of 23	NP_001289698.1	Q8TEW8-1
	PARD3B	NM_152526.6		c.365T>C	p.Ile122Thr	missense	Exon 3 of 22	NP_689739.4
	PARD3B	NM_057177.7		c.365T>C	p.Ile122Thr	missense	Exon 3 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.365T>C	p.Ile122Thr	missense	Exon 3 of 23	ENSP00000385848.2	Q8TEW8-1
	PARD3B	ENST00000358768.6	TSL:1	c.365T>C	p.Ile122Thr	missense	Exon 3 of 22	ENSP00000351618.2	Q8TEW8-2
	PARD3B	ENST00000351153.5	TSL:1	c.365T>C	p.Ile122Thr	missense	Exon 3 of 22	ENSP00000317261.2	Q8TEW8-6

Frequencies

GnomAD3 genomes AF: 0.00198 AC: 301 AN: 152188 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000338

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.00216

Gnomad ASJ AF: 0.00346

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00207

Gnomad FIN AF: 0.0000942

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00325

Gnomad OTH AF: 0.00335

GnomAD2 exomes AF: 0.00228 AC: 567 AN: 249208 AF XY: 0.00253

Gnomad AFR exome AF: 0.000581

Gnomad AMR exome AF: 0.00163

Gnomad ASJ exome AF: 0.00407

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000186

Gnomad NFE exome AF: 0.00348

Gnomad OTH exome AF: 0.00298

GnomAD4 exome AF: 0.00243 AC: 3558 AN: 1461516 Hom.: 9 Cov.: 32 AF XY: 0.00249 AC XY: 1810 AN XY: 727064

African (AFR) AF: 0.000418 AC: 14 AN: 33454

American (AMR) AF: 0.00166 AC: 74 AN: 44694

Ashkenazi Jewish (ASJ) AF: 0.00379 AC: 99 AN: 26128

East Asian (EAS) AF: 0.00 AC: 0 AN: 39694

South Asian (SAS) AF: 0.00155 AC: 134 AN: 86250

European-Finnish (FIN) AF: 0.000393 AC: 21 AN: 53376

Middle Eastern (MID) AF: 0.00572 AC: 33 AN: 5766

European-Non Finnish (NFE) AF: 0.00274 AC: 3050 AN: 1111792

Other (OTH) AF: 0.00220 AC: 133 AN: 60362

GnomAD4 genome AF: 0.00197 AC: 300 AN: 152306 Hom.: 0 Cov.: 33 AF XY: 0.00204 AC XY: 152 AN XY: 74468

African (AFR) AF: 0.000337 AC: 14 AN: 41562

American (AMR) AF: 0.00216 AC: 33 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00346 AC: 12 AN: 3468

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5186

South Asian (SAS) AF: 0.00207 AC: 10 AN: 4824

European-Finnish (FIN) AF: 0.0000942 AC: 1 AN: 10620

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

European-Non Finnish (NFE) AF: 0.00325 AC: 221 AN: 68038

Other (OTH) AF: 0.00331 AC: 7 AN: 2114

Alfa AF: 0.00293 Hom.: 5

Bravo AF: 0.00201

TwinsUK AF: 0.00216 AC: 8

ALSPAC AF: 0.00208 AC: 8

ESP6500AA AF: 0.000537 AC: 2

ESP6500EA AF: 0.00256 AC: 21

ExAC AF: 0.00227 AC: 274

EpiCase AF: 0.00414

EpiControl AF: 0.00480

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	PARD3B-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.77
BayesDel_addAF	Benign	-0.018	T
BayesDel_noAF	Pathogenic	0.20
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.21	T
Eigen	Pathogenic	0.71
Eigen_PC	Pathogenic	0.69
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.86	D
M_CAP	Benign	0.055	D
MetaRNN	Benign	0.010	T
MetaSVM	Uncertain	-0.22	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		5.5
PrimateAI	Uncertain	0.66	T
PROVEAN	Uncertain	-4.1	D
REVEL	Uncertain	0.41
Sift	Uncertain	0.0010	D
Sift4G	Pathogenic	0.0010	D
Polyphen		0.97	D
Vest4		0.97
MVP		0.86
MPC		0.15
ClinPred		0.042	T
GERP RS		5.8
PromoterAI		0.011	Neutral
Varity_R		0.65
gMVP		0.65
Mutation Taster		=99/1	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: rs74648966; hg19: chr2-205830017;