rs730882137

chr4-168878150-TCGCCCC-Tchr4-168878150-TCGCCCC-TCGCCCCCGCCCCchr4-168878150-TCGCCCC-TCGCCCCCGCCCCCGCCCC

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The ENST00000507735.6(PALLD):c.270_275del(p.Pro93_Pro94del) variant causes a inframe deletion change. The variant allele was found at a frequency of 0.00007 in 1,486,674 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000087 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000068 (0 hom.)
• Consequence: PALLD ENST00000507735.6 inframe_deletion
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.33

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 Likely_benign. Variant got -4 ACMG points.

• BS2: High AC in GnomAd at 13 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PALLD	NM_001166108.2	c.1965-12761_1965-12756del		intron_variant		ENST00000505667.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PALLD	ENST00000505667.6	c.1965-12761_1965-12756del		intron_variant		1	NM_001166108.2	A2

Frequencies

GnomAD3 genomes AF: 0.0000869 AC: 13 AN: 149544 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000497

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000132

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000213

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000119

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.0000890 AC: 8 AN: 89912 Hom.: 0 AF XY: 0.0000988 AC XY: 5 AN XY: 50616

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000382

Gnomad SAS exome AF: 0.000111

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000907

Gnomad OTH exome AF: 0.000371

GnomAD4 exome AF: 0.0000681 AC: 91 AN: 1337022 Hom.: 0 AF XY: 0.0000728 AC XY: 48 AN XY: 659012

Gnomad4 AFR exome AF: 0.0000741

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.0000424

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000268

Gnomad4 FIN exome AF: 0.0000905

Gnomad4 NFE exome AF: 0.0000709

Gnomad4 OTH exome AF: 0.000144

GnomAD4 genome AF: 0.0000869 AC: 13 AN: 149652 Hom.: 0 Cov.: 32 AF XY: 0.0000820 AC XY: 6 AN XY: 73164

Gnomad4 AFR AF: 0.0000495

Gnomad4 AMR AF: 0.000132

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000213

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000119

Gnomad4 OTH AF: 0.00

Bravo AF: 0.0000869

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Pancreatic adenocarcinoma Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Invitae

May 08, 2023

In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. ClinVar contains an entry for this variant (Variation ID: 476387). This variant has not been reported in the literature in individuals affected with PALLD-related conditions. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant, c.270_275del, results in the deletion of 2 amino acid(s) of the PALLD protein (p.Pro93_Pro94del), but otherwise preserves the integrity of the reading frame. -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs730882137; hg19: chr4-169799301;