4-168928326-TAAAA-TAAAAAAAA

Variant names:

• chr4-168928326-T-TAAAA
• rs398064261
• ENST00000507699.1:n.3745_3748dupAAAA

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The ENST00000507699.1(PALLD):​n.3745_3748dupAAAA variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 0)
  • Exomes 𝑓: 0.000036 (0 hom.)
• Consequence: PALLD ENST00000507699.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.04
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PALLD	NM_001166108.2	c.*2153_*2156dupAAAA		3_prime_UTR_variant	Exon 22 of 22	ENST00000505667.6	NP_001159580.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PALLD	ENST00000505667.6	c.*2153_*2156dupAAAA		3_prime_UTR_variant	Exon 22 of 22	1	NM_001166108.2	ENSP00000425556.1

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD4 exome AF: 0.0000356 AC: 1 AN: 28070 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 12878

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00104 AC: 1 AN: 960

American (AMR) AF: 0.00 AC: 0 AN: 614

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 1778

East Asian (EAS) AF: 0.00 AC: 0 AN: 5512

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

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 442

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 172

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 16064

Other (OTH) AF: 0.00 AC: 0 AN: 2300

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		3.0

Splicing

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

Other links and lift over

dbSNP: rs398064261; hg19: chr4-169849477;