Genetic Variant ENST00000507735.6:c.295A>C (chr4-168878186-A-C) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The ENST00000507735.6(PALLD):c.295A>C(p.Thr99Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. 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 Benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T99R) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.000089 ( 0 hom., cov: 30)

Exomes 𝑓: 0.0000085 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

PALLD
ENST00000507735.6 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.937

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 Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.06601599).

BP6

Variant 4-168878186-A-C is Benign according to our data. Variant chr4-168878186-A-C is described in ClinVar as [Benign]. Clinvar id is 219732.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PALLD	NM_001166108.2 link	c.1965-12736A>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
PALLD	ENST00000505667.6 link	c.1965-12736A>C		intron_variant	Intron 10 of 21	1	NM_001166108.2	ENSP00000425556.1		Q8WX93-9

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

101166

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.000238

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000102

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:

0.0000202

Gnomad OTH

AF:

0.000732

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000851

AC:

AN:

1175768

Hom.:

Cov.:

AF XY:

0.00000691

AC XY:

AN XY:

578994

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:

0.0000143

Gnomad4 FIN exome

AF:

0.0000560

Gnomad4 NFE exome

AF:

0.00000735

Gnomad4 OTH exome

AF:

0.0000224

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000889

AC:

AN:

101188

Hom.:

Cov.:

AF XY:

0.0000407

AC XY:

AN XY:

49104

show subpopulations

Gnomad4 AFR

AF:

0.000238

Gnomad4 AMR

AF:

0.000102

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000202

Gnomad4 OTH

AF:

0.000727

Alfa

AF:

0.0247

Hom.:

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Pancreatic adenocarcinoma

Benign:1

Oct 30, 2015

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.53

CADD

Benign

3.4

DANN

Benign

0.48

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.41

LIST_S2

Benign

0.54

M_CAP

Benign

0.036

MetaRNN

Benign

0.066

MetaSVM

Benign

-1.1

PROVEAN

Benign

-1.2

REVEL

Benign

0.074

Sift

Benign

0.32

Sift4G

Benign

0.54

Vest4

0.10

MVP

0.11

ClinPred

0.045

GERP RS

-3.9

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