Variant 4-168878233-A-ACCG details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 1P and 16B. PM4_SupportingBP6_Very_StrongBS1BS2

The ENST00000507735.6(PALLD):c.347_349dup(p.Pro116dup) variant causes a inframe insertion change. The variant allele was found at a frequency of 0.00166 in 1,497,616 control chromosomes in the GnomAD database, including 36 homozygotes. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0099 ( 19 hom., cov: 32)

Exomes 𝑓: 0.00080 ( 17 hom. )

Consequence

PALLD
ENST00000507735.6 inframe_insertion

Scores

Not classified

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 5.32

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

PM4

Nonframeshift variant in NON repetitive region in ENST00000507735.6. Strenght limited to Supporting due to length of the change: 1aa.

BP6

Variant 4-168878233-A-ACCG is Benign according to our data. Variant chr4-168878233-A-ACCG is described in ClinVar as [Benign]. Clinvar id is 416233.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00987 (1399/141794) while in subpopulation AFR AF= 0.0346 (1304/37698). AF 95% confidence interval is 0.033. There are 19 homozygotes in gnomad4. There are 668 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 1399 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PALLD	NM_001166108.2 linkuse as main transcript	c.1965-12684_1965-12682dup		intron_variant		ENST00000505667.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PALLD	ENST00000505667.6 linkuse as main transcript	c.1965-12684_1965-12682dup		intron_variant		1	NM_001166108.2	A2	Q8WX93-9

Frequencies

GnomAD3 genomes

AF:

0.00983

AC:

1393

AN:

141710

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0345

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00451

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000240

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000260

Gnomad OTH

AF:

0.00669

GnomAD3 exomes

AF:

0.00111

AC:

127

AN:

113988

Hom.:

AF XY:

0.000715

AC XY:

AN XY:

62916

show subpopulations

Gnomad AFR exome

AF:

0.0256

Gnomad AMR exome

AF:

0.00116

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000489

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000702

Gnomad OTH exome

AF:

0.00172

GnomAD4 exome

AF:

0.000800

AC:

1084

AN:

1355822

Hom.:

Cov.:

AF XY:

0.000670

AC XY:

448

AN XY:

669068

show subpopulations

Gnomad4 AFR exome

AF:

0.0297

Gnomad4 AMR exome

AF:

0.00174

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000520

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000347

Gnomad4 OTH exome

AF:

0.00208

GnomAD4 genome

AF:

0.00987

AC:

1399

AN:

141794

Hom.:

Cov.:

AF XY:

0.00970

AC XY:

668

AN XY:

68884

show subpopulations

Gnomad4 AFR

AF:

0.0346

Gnomad4 AMR

AF:

0.00450

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000240

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000260

Gnomad4 OTH

AF:

0.00663

Alfa

AF:

0.00554

Hom.:

Asia WGS

AF:

0.00145

AC:

AN:

3466

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Pancreatic adenocarcinoma

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 27, 2024

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 03, 2015

- -

PALLD-related disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 10, 2019

This 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

Splicing

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