4-168497281-T-C

Position:

• chr4-168497281-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001166108.2(PALLD):​c.-83+87T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0967 in 152,070 control chromosomes in the GnomAD database, including 804 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.097 (804 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: PALLD NM_001166108.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.00700

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]

DDX60L (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 4-168497281-T-C is Benign according to our data. Variant chr4-168497281-T-C is described in ClinVar as [Benign]. Clinvar id is 1226420.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.107 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PALLD	NM_001166108.2	c.-83+87T>C		intron_variant		ENST00000505667.6	NP_001159580.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PALLD	ENST00000505667.6	c.-83+87T>C		intron_variant		1	NM_001166108.2	ENSP00000425556.1

Frequencies

GnomAD3 genomes AF: 0.0968 AC: 14703 AN: 151952 Hom.: 804 Cov.: 32

Gnomad AFR AF: 0.0897

Gnomad AMI AF: 0.156

Gnomad AMR AF: 0.0535

Gnomad ASJ AF: 0.0432

Gnomad EAS AF: 0.0333

Gnomad SAS AF: 0.0525

Gnomad FIN AF: 0.176

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.109

Gnomad OTH AF: 0.0837

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0967 AC: 14705 AN: 152070 Hom.: 804 Cov.: 32 AF XY: 0.0967 AC XY: 7184 AN XY: 74322

Gnomad4 AFR AF: 0.0896

Gnomad4 AMR AF: 0.0533

Gnomad4 ASJ AF: 0.0432

Gnomad4 EAS AF: 0.0336

Gnomad4 SAS AF: 0.0526

Gnomad4 FIN AF: 0.176

Gnomad4 NFE AF: 0.109

Gnomad4 OTH AF: 0.0828

Alfa AF: 0.106 Hom.: 172

Bravo AF: 0.0881

Asia WGS AF: 0.0480 AC: 166 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 23, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	5.4
DANN	Benign	0.63

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: rs62333818; hg19: chr4-169418432;