chr4-168928326-TAA-T

Variant names:

• chr4-168928326-TAA-T
• rs398064261
• NM_001166108.2:c.*2155_*2156delAA

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_001166108.2(PALLD):​c.*2155_*2156delAA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00125 in 179,460 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★★).

• Frequency:
  • Genomes: 𝑓 0.0012 (1 hom., cov: 0)
  • Exomes 𝑓: 0.0018 (0 hom.)
• Consequence: PALLD NM_001166108.2 3_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, multiple submitters, no conflicts U:2
• Conservation: PhyloP100: 3.04
• Publications: 1 publications found

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

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BS2: High AC in GnomAd4 at 175 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001166108.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PALLD	NM_001166108.2	MANE Select	c.*2155_*2156delAA		3_prime_UTR	Exon 22 of 22	NP_001159580.1	Q8WX93-9
	PALLD	NM_016081.4		c.*2155_*2156delAA		3_prime_UTR	Exon 21 of 21	NP_057165.3
	PALLD	NM_001166109.2		c.*1950_*1951delAA		3_prime_UTR	Exon 19 of 19	NP_001159581.1	Q8WX93-8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PALLD	ENST00000505667.6	TSL:1 MANE Select	c.*2155_*2156delAA		3_prime_UTR	Exon 22 of 22	ENSP00000425556.1	Q8WX93-9
	PALLD	ENST00000261509.10	TSL:1	c.*2155_*2156delAA		3_prime_UTR	Exon 21 of 21	ENSP00000261509.6	Q8WX93-2
	PALLD	ENST00000507735.6	TSL:1	c.*1950_*1951delAA		3_prime_UTR	Exon 12 of 12	ENSP00000424016.1	Q8WX93-4

Frequencies

GnomAD3 genomes AF: 0.00116 AC: 175 AN: 151352 Hom.: 1 Cov.: 0

Gnomad AFR AF: 0.00105

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00125

Gnomad ASJ AF: 0.000865

Gnomad EAS AF: 0.000387

Gnomad SAS AF: 0.00104

Gnomad FIN AF: 0.000191

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00146

Gnomad OTH AF: 0.000961

GnomAD4 exome AF: 0.00179 AC: 50 AN: 27994 Hom.: 0 AF XY: 0.00202 AC XY: 26 AN XY: 12852

African (AFR) AF: 0.00208 AC: 2 AN: 960

American (AMR) AF: 0.00328 AC: 2 AN: 610

Ashkenazi Jewish (ASJ) AF: 0.00339 AC: 6 AN: 1772

East Asian (EAS) AF: 0.000911 AC: 5 AN: 5490

South Asian (SAS) AF: 0.00 AC: 0 AN: 228

European-Finnish (FIN) AF: 0.00226 AC: 1 AN: 442

Middle Eastern (MID) AF: 0.00581 AC: 1 AN: 172

European-Non Finnish (NFE) AF: 0.00181 AC: 29 AN: 16024

Other (OTH) AF: 0.00174 AC: 4 AN: 2296

GnomAD4 genome AF: 0.00116 AC: 175 AN: 151466 Hom.: 1 Cov.: 0 AF XY: 0.00105 AC XY: 78 AN XY: 74010

African (AFR) AF: 0.00105 AC: 43 AN: 41090

American (AMR) AF: 0.00125 AC: 19 AN: 15236

Ashkenazi Jewish (ASJ) AF: 0.000865 AC: 3 AN: 3470

East Asian (EAS) AF: 0.000388 AC: 2 AN: 5152

South Asian (SAS) AF: 0.00104 AC: 5 AN: 4810

European-Finnish (FIN) AF: 0.000191 AC: 2 AN: 10474

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00146 AC: 99 AN: 67926

Other (OTH) AF: 0.000951 AC: 2 AN: 2104

Alfa AF: 0.00131 Hom.: 1399

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	1	-	Carcinoma of pancreas (1)
-	1	-	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		3.0
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs398064261; hg19: chr4-169849477;