rs62333013

Positions:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000507735.6(PALLD):c.406A>G(p.Ser136Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.613 in 1,525,872 control chromosomes in the GnomAD database, including 295,098 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/14 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S136R) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.51 ( 22843 hom., cov: 33)

Exomes 𝑓: 0.62 ( 272255 hom. )

Consequence

PALLD
ENST00000507735.6 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.339

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]

PALLD links:

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]

CBR4 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=3.1354703E-6).

BP6

Variant 4-168878297-A-G is Benign according to our data. Variant chr4-168878297-A-G is described in ClinVar as [Benign]. Clinvar id is 182793.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.645 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PALLD	NM_001166108.2 linkuse as main transcript	c.1965-12625A>G		intron_variant		ENST00000505667.6	NP_001159580.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PALLD	ENST00000505667.6 linkuse as main transcript	c.1965-12625A>G		intron_variant		1	NM_001166108.2	ENSP00000425556	A2	Q8WX93-9

Frequencies

GnomAD3 genomes

AF:

0.507

AC:

77069

AN:

151876

Hom.:

22832

Cov.:

show subpopulations

Gnomad AFR

AF:

0.177

Gnomad AMI

AF:

0.604

Gnomad AMR

AF:

0.554

Gnomad ASJ

AF:

0.612

Gnomad EAS

AF:

0.536

Gnomad SAS

AF:

0.663

Gnomad FIN

AF:

0.730

Gnomad MID

AF:

0.532

Gnomad NFE

AF:

0.643

Gnomad OTH

AF:

0.525

GnomAD3 exomes

AF:

0.613

AC:

74166

AN:

121080

Hom.:

23566

AF XY:

0.618

AC XY:

41053

AN XY:

66452

show subpopulations

Gnomad AFR exome

AF:

0.136

Gnomad AMR exome

AF:

0.626

Gnomad ASJ exome

AF:

0.621

Gnomad EAS exome

AF:

0.523

Gnomad SAS exome

AF:

0.661

Gnomad FIN exome

AF:

0.734

Gnomad NFE exome

AF:

0.640

Gnomad OTH exome

AF:

0.602

GnomAD4 exome

AF:

0.624

AC:

857519

AN:

1373882

Hom.:

272255

Cov.:

AF XY:

0.627

AC XY:

424889

AN XY:

677634

show subpopulations

Gnomad4 AFR exome

AF:

0.152

Gnomad4 AMR exome

AF:

0.620

Gnomad4 ASJ exome

AF:

0.617

Gnomad4 EAS exome

AF:

0.535

Gnomad4 SAS exome

AF:

0.664

Gnomad4 FIN exome

AF:

0.730

Gnomad4 NFE exome

AF:

0.636

Gnomad4 OTH exome

AF:

0.595

GnomAD4 genome

AF:

0.507

AC:

77091

AN:

151990

Hom.:

22843

Cov.:

AF XY:

0.515

AC XY:

38272

AN XY:

74310

show subpopulations

Gnomad4 AFR

AF:

0.176

Gnomad4 AMR

AF:

0.554

Gnomad4 ASJ

AF:

0.612

Gnomad4 EAS

AF:

0.536

Gnomad4 SAS

AF:

0.664

Gnomad4 FIN

AF:

0.730

Gnomad4 NFE

AF:

0.643

Gnomad4 OTH

AF:

0.527

Alfa

AF:

0.597

Hom.:

6471

Bravo

AF:

0.479

TwinsUK

AF:

0.656

AC:

2431

ALSPAC

AF:

0.631

AC:

2433

ExAC

AF:

0.540

AC:

8133

Asia WGS

AF:

0.622

AC:

2160

AN:

3472

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Mar 28, 2016	Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -
Benign, criteria provided, single submitter	clinical testing	Ambry Genetics	Jul 30, 2020	This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Pancreatic cancer, susceptibility to, 1

Benign:1

Benign, criteria provided, single submitter

clinical testing

KCCC/NGS Laboratory, Kuwait Cancer Control Center

Jul 07, 2023

- -

Pancreatic adenocarcinoma

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.70

BayesDel_noAF

Benign

-0.63

CADD

Benign

1.9

DANN

Benign

0.75

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.039

LIST_S2

Benign

0.34

MetaRNN

Benign

0.0000031

MetaSVM

Benign

-0.96

MutationTaster

Benign

1.0

P;P;P;P;P

PROVEAN

Benign

-0.94

REVEL

Benign

0.094

Sift

Benign

0.75

Sift4G

Benign

0.37

Vest4

0.015

ClinPred

0.0034

GERP RS

-5.0

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over