rs374453548

Variant names:

• chr2-205104433-C-A
• rs374453548
• NM_001302769.2:c.512C>A

Your query was ambiguous. Multiple possible variants found:

• chr2-205104433-C-A
• chr2-205104433-C-G
• chr2-205104433-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001302769.2(PARD3B):​c.512C>A​(p.Thr171Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PARD3B NM_001302769.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.32

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.0650973).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PARD3B	NM_001302769.2	c.512C>A	p.Thr171Lys	missense_variant	Exon 5 of 23	ENST00000406610.7	NP_001289698.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PARD3B	ENST00000406610.7	c.512C>A	p.Thr171Lys	missense_variant	Exon 5 of 23	1	NM_001302769.2	ENSP00000385848.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1443218 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 719090

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

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.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.099
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	16
DANN	Benign	0.81
DEOGEN2	Benign	0.0052	T;T;.;.;.;.;.;T
Eigen	Benign	-0.64
Eigen_PC	Benign	-0.60
FATHMM_MKL	Benign	0.51	D
LIST_S2	Benign	0.81	T;T;T;T;T;T;T;T
M_CAP	Benign	0.0067	T
MetaRNN	Benign	0.065	T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Uncertain	2.3	M;.;M;M;M;.;.;.
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-1.3	N;.;N;N;N;.;.;.
REVEL	Benign	0.029
Sift	Benign	0.10	T;.;T;T;T;.;.;.
Sift4G	Benign	0.33	T;T;T;T;T;T;T;T
Polyphen		0.27	B;.;B;.;B;.;.;.
Vest4		0.28
MutPred		0.26		Gain of ubiquitination at T171 (P = 0.0045);Gain of ubiquitination at T171 (P = 0.0045);Gain of ubiquitination at T171 (P = 0.0045);Gain of ubiquitination at T171 (P = 0.0045);Gain of ubiquitination at T171 (P = 0.0045);.;.;.;
MVP		0.38
MPC		0.032
ClinPred		0.10	T
GERP RS		1.4
Varity_R		0.049
gMVP		0.26

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs374453548; hg19: chr2-205969157;