rs863224385

chr4-168878167-A-Cchr4-168878167-A-G

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP6_Very_Strong BP7

The ENST00000507735.6(PALLD):c.276A>C(p.Pro92=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0018 (0 hom., cov: 29)
  • Exomes 𝑓: 0.0079 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PALLD ENST00000507735.6 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.780

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]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.62).
• BP6: Variant 4-168878167-A-C is Benign according to our data. Variant chr4-168878167-A-C is described in ClinVar as [Likely_benign]. Clinvar id is 215806.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.78 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PALLD	NM_001166108.2	c.1965-12755A>C		intron_variant		ENST00000505667.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PALLD	ENST00000505667.6	c.1965-12755A>C		intron_variant		1	NM_001166108.2	A2

Frequencies

GnomAD3 genomes AF: 0.00 AC: 169 AN: 93584 Hom.: 0 Cov.: 29 FAILED QC

Gnomad AFR AF: 0.00339

Gnomad AMI AF: 0.00190

Gnomad AMR AF: 0.00103

Gnomad ASJ AF: 0.000411

Gnomad EAS AF: 0.000613

Gnomad SAS AF: 0.00197

Gnomad FIN AF: 0.00361

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00113

Gnomad OTH AF: 0.00153

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00787 AC: 5710 AN: 725918 Hom.: 0 Cov.: 36 AF XY: 0.00781 AC XY: 2806 AN XY: 359264

Gnomad4 AFR exome AF: 0.0131

Gnomad4 AMR exome AF: 0.0426

Gnomad4 ASJ exome AF: 0.0123

Gnomad4 EAS exome AF: 0.00529

Gnomad4 SAS exome AF: 0.0137

Gnomad4 FIN exome AF: 0.0212

Gnomad4 NFE exome AF: 0.00602

Gnomad4 OTH exome AF: 0.0116

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00181 AC: 169 AN: 93620 Hom.: 0 Cov.: 29 AF XY: 0.00164 AC XY: 75 AN XY: 45738

Gnomad4 AFR AF: 0.00338

Gnomad4 AMR AF: 0.00102

Gnomad4 ASJ AF: 0.000411

Gnomad4 EAS AF: 0.000614

Gnomad4 SAS AF: 0.00197

Gnomad4 FIN AF: 0.00361

Gnomad4 NFE AF: 0.00113

Gnomad4 OTH AF: 0.00152

Alfa AF: 0.0482 Hom.: 0

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Pancreatic adenocarcinoma Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Aug 04, 2023

- -

PALLD-related disorder Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Nov 01, 2021

This variant is classified as likely 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_noAF	Benign	-0.62
Cadd	Benign	8.7
Dann	Benign	0.43

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

Other links and lift over

dbSNP: rs863224385; hg19: chr4-169799318;