rs550499593

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The ENST00000507735.6(PALLD):ā€‹c.121C>Gā€‹(p.Pro41Ala) variant causes a missense change. The variant allele was found at a frequency of 0.000431 in 1,497,448 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/14 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (ā˜…). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P41R) has been classified as Uncertain significance.

Frequency

Genomes: š‘“ 0.00068 ( 2 hom., cov: 32)
Exomes š‘“: 0.00040 ( 5 hom. )

Consequence

PALLD
ENST00000507735.6 missense

Scores

2
12

Clinical Significance

Benign criteria provided, single submitter B:2

Conservation

PhyloP100: 5.34
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 Benign. Variant got -14 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.0037773848).
BP6
Variant 4-168878012-C-G is Benign according to our data. Variant chr4-168878012-C-G is described in ClinVar as [Benign]. Clinvar id is 135995.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.000684 (104/152038) while in subpopulation EAS AF= 0.0194 (100/5158). AF 95% confidence interval is 0.0163. There are 2 homozygotes in gnomad4. There are 64 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High AC in GnomAd4 at 104 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
PALLDNM_001166108.2 linkuse as main transcriptc.1965-12910C>G intron_variant ENST00000505667.6 NP_001159580.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
PALLDENST00000505667.6 linkuse as main transcriptc.1965-12910C>G intron_variant 1 NM_001166108.2 ENSP00000425556 A2Q8WX93-9

Frequencies

GnomAD3 genomes
AF:
0.000691
AC:
105
AN:
151930
Hom.:
2
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000656
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.0195
Gnomad SAS
AF:
0.000620
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00121
AC:
115
AN:
94802
Hom.:
0
AF XY:
0.00122
AC XY:
65
AN XY:
53380
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000506
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0178
Gnomad SAS exome
AF:
0.000732
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.000347
GnomAD4 exome
AF:
0.000403
AC:
542
AN:
1345410
Hom.:
5
Cov.:
31
AF XY:
0.000432
AC XY:
287
AN XY:
663666
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000635
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0149
Gnomad4 SAS exome
AF:
0.000672
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.000516
GnomAD4 genome
AF:
0.000684
AC:
104
AN:
152038
Hom.:
2
Cov.:
32
AF XY:
0.000861
AC XY:
64
AN XY:
74330
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.0000655
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.0194
Gnomad4 SAS
AF:
0.000621
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000189
Hom.:
1
Bravo
AF:
0.000722
ExAC
AF:
0.000420
AC:
8
Asia WGS
AF:
0.00440
AC:
15
AN:
3424

ClinVar

Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Pancreatic adenocarcinoma Benign:1
Benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpJan 02, 2024- -
PALLD-related disorder Benign:1
Benign, no assertion criteria providedclinical testingPreventionGenetics, part of Exact SciencesDec 18, 2019This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
-0.42
T
BayesDel_noAF
Benign
-0.36
CADD
Benign
18
DANN
Benign
0.68
Eigen
Benign
-0.42
Eigen_PC
Benign
-0.40
FATHMM_MKL
Uncertain
0.85
D
LIST_S2
Benign
0.54
T
MetaRNN
Benign
0.0038
T
MetaSVM
Benign
-1.0
T
MutationTaster
Benign
1.0
D;D;D;N;N
PROVEAN
Benign
-0.91
N
REVEL
Benign
0.080
Sift
Benign
0.25
T
Sift4G
Uncertain
0.059
T
Vest4
0.11
MVP
0.44
ClinPred
0.019
T
GERP RS
3.8
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.8

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: rs550499593; hg19: chr4-169799163; API