10-34111354-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001184785.2(PARD3):​c.3877C>G​(p.Gln1293Glu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts 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: 32)

Consequence

PARD3
NM_001184785.2 missense

Scores

3
5
11

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.59
Variant links:
Genes affected
PARD3 (HGNC:16051): (par-3 family cell polarity regulator) This gene encodes a member of the PARD protein family. PARD family members interact with other PARD family members and other proteins; they affect asymmetrical cell division and direct polarized cell growth. Multiple alternatively spliced transcript variants have been described for this gene. [provided by RefSeq, Oct 2011]

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ACMG classification

Classification made for transcript

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=0.263497).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
PARD3NM_001184785.2 linkuse as main transcriptc.3877C>G p.Gln1293Glu missense_variant 25/25 ENST00000374788.8 NP_001171714.1 Q8TEW0-2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
PARD3ENST00000374788.8 linkuse as main transcriptc.3877C>G p.Gln1293Glu missense_variant 25/251 NM_001184785.2 ENSP00000363920.3 Q8TEW0-2

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsJul 05, 2024The c.3886C>G (p.Q1296E) alteration is located in exon 25 (coding exon 25) of the PARD3 gene. This alteration results from a C to G substitution at nucleotide position 3886, causing the glutamine (Q) at amino acid position 1296 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.13
BayesDel_addAF
Benign
-0.068
T
BayesDel_noAF
Benign
-0.34
CADD
Uncertain
24
DANN
Uncertain
1.0
DEOGEN2
Benign
0.15
.;.;T;.;.;.;.;.
Eigen
Uncertain
0.66
Eigen_PC
Pathogenic
0.71
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Pathogenic
0.98
D;D;D;D;D;D;D;D
M_CAP
Benign
0.014
T
MetaRNN
Benign
0.26
T;T;T;T;T;T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
1.0
.;.;L;.;.;.;.;.
PrimateAI
Uncertain
0.60
T
PROVEAN
Benign
-1.4
N;N;N;N;N;N;N;N
REVEL
Uncertain
0.30
Sift
Uncertain
0.013
D;D;D;D;D;D;D;D
Sift4G
Benign
0.18
T;D;D;D;T;D;T;D
Polyphen
0.89
P;.;D;D;D;D;D;.
Vest4
0.34
MutPred
0.14
.;.;Gain of ubiquitination at K1294 (P = 0.0248);.;.;.;.;.;
MVP
0.51
MPC
0.47
ClinPred
0.93
D
GERP RS
5.3
Varity_R
0.34
gMVP
0.50

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr10-34400282; API