rs878854266

Variant summary

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

The NM_001166110.2(PALLD):ā€‹c.496A>Cā€‹(p.Thr166Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000198 in 151,646 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/15 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…ā˜…).

Frequency

Genomes: š‘“ 0.000020 ( 0 hom., cov: 32)
Exomes š‘“: 7.5e-7 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

PALLD
NM_001166110.2 missense

Scores

15

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:2

Conservation

PhyloP100: 3.19
Variant links:
Genes affected
PALLD (HGNC:17068): (palladin, cytoskeletal associated protein) This gene encodes a cytoskeletal protein that is required for organizing the actin cytoskeleton. The protein is a component of actin-containing microfilaments, and it is involved in the control of cell shape, adhesion, and contraction. Polymorphisms in this gene are associated with a susceptibility to pancreatic cancer type 1, and also with a risk for myocardial infarction. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2009]
CBR4 (HGNC:25891): (carbonyl reductase 4) Enables several functions, including 3-oxoacyl-[acyl-carrier-protein] reductase (NADPH) activity; NADPH binding activity; and NADPH dehydrogenase (quinone) activity. Involved in fatty acid biosynthetic process; glycoside metabolic process; and protein tetramerization. Located in mitochondrial matrix. Part of oxidoreductase complex. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

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=0.094516546).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PALLDNM_001166108.2 linkc.1965-12535A>C intron_variant Intron 10 of 21 ENST00000505667.6 NP_001159580.1 Q8WX93-9

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
PALLDENST00000505667.6 linkc.1965-12535A>C intron_variant Intron 10 of 21 1 NM_001166108.2 ENSP00000425556.1 Q8WX93-9

Frequencies

GnomAD3 genomes
AF:
0.0000198
AC:
3
AN:
151646
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000727
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
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:
0.00
Gnomad OTH
AF:
0.00
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
AF:
7.46e-7
AC:
1
AN:
1340906
Hom.:
0
Cov.:
35
AF XY:
0.00
AC XY:
0
AN XY:
659390
show subpopulations
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:
9.44e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000198
AC:
3
AN:
151646
Hom.:
0
Cov.:
32
AF XY:
0.0000270
AC XY:
2
AN XY:
74036
show subpopulations
Gnomad4 AFR
AF:
0.0000727
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsDec 07, 2024The p.T166P variant (also known as c.496A>C), located in coding exon 1 of the PALLD gene, results from an A to C substitution at nucleotide position 496. The threonine at codon 166 is replaced by proline, an amino acid with highly similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Based on the available evidence, the clinical significance of this variant remains unclear. -
Pancreatic adenocarcinoma Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpOct 26, 2022This variant is present in population databases (no rsID available, gnomAD 0.02%). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. ClinVar contains an entry for this variant (Variation ID: 238612). This variant has not been reported in the literature in individuals affected with PALLD-related conditions. This sequence change replaces threonine, which is neutral and polar, with proline, which is neutral and non-polar, at codon 166 of the PALLD protein (p.Thr166Pro). -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
-0.10
T
BayesDel_noAF
Benign
-0.38
CADD
Benign
19
DANN
Benign
0.92
Eigen
Benign
-0.45
Eigen_PC
Benign
-0.30
FATHMM_MKL
Benign
0.57
D
LIST_S2
Benign
0.54
T
M_CAP
Benign
0.045
D
MetaRNN
Benign
0.095
T
MetaSVM
Benign
-1.0
T
PROVEAN
Benign
-0.35
N
REVEL
Benign
0.12
Sift
Benign
0.27
T
Sift4G
Benign
0.70
T
Vest4
0.11
MVP
0.38
ClinPred
0.15
T
GERP RS
2.6

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs878854266; hg19: chr4-169799538; API