4-168511315-CTT-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001166108.2(PALLD):c.-82-107_-82-106del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.299 in 587,168 control chromosomes in the GnomAD database, including 27,086 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.29 (6652 hom., cov: 0)
  • Exomes 𝑓: 0.30 (20434 hom.)
• Consequence: PALLD NM_001166108.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.334

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]

LOC107986198 (HGNC:):

DDX60L (HGNC:26429): (DExD/H-box 60 like) This gene encodes a member of the DExD/H-box helicase family of proteins, a subset of the super family 2 helicases. Members of the DExD/H-box helicase family share a conserved functional core comprised of two RecA-like globular domains. These domains contain conserved motifs that mediate ATP binding, ATP hydrolysis, nucleic acid binding, and RNA unwinding. In addition to functions in RNA metabolism, members of this family are involved in anti-viral immunity and act as cytosolic sensors of viral nucleic acids. The protein encoded by this gene has been shown to inhibit hepatitis C virus replication in response to interferon stimulation in cell culture. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2016]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 4-168511315-CTT-C is Benign according to our data. Variant chr4-168511315-CTT-C is described in ClinVar as [Benign]. Clinvar id is 1289336.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.326 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PALLD	NM_001166108.2	c.-82-107_-82-106del		intron_variant		ENST00000505667.6
LOC107986198	XR_001741448.3	n.281-18432_281-18431del		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PALLD	ENST00000505667.6	c.-82-107_-82-106del		intron_variant		1	NM_001166108.2	A2

Frequencies

GnomAD3 genomes AF: 0.294 AC: 44664 AN: 151862 Hom.: 6645 Cov.: 0

Gnomad AFR AF: 0.249

Gnomad AMI AF: 0.433

Gnomad AMR AF: 0.242

Gnomad ASJ AF: 0.281

Gnomad EAS AF: 0.191

Gnomad SAS AF: 0.223

Gnomad FIN AF: 0.395

Gnomad MID AF: 0.272

Gnomad NFE AF: 0.330

Gnomad OTH AF: 0.280

GnomAD4 exome AF: 0.301 AC: 131070 AN: 435188 Hom.: 20434 AF XY: 0.297 AC XY: 68263 AN XY: 230090

Gnomad4 AFR exome AF: 0.249

Gnomad4 AMR exome AF: 0.211

Gnomad4 ASJ exome AF: 0.296

Gnomad4 EAS exome AF: 0.196

Gnomad4 SAS exome AF: 0.228

Gnomad4 FIN exome AF: 0.392

Gnomad4 NFE exome AF: 0.326

Gnomad4 OTH exome AF: 0.295

GnomAD4 genome AF: 0.294 AC: 44693 AN: 151980 Hom.: 6652 Cov.: 0 AF XY: 0.293 AC XY: 21765 AN XY: 74262

Gnomad4 AFR AF: 0.250

Gnomad4 AMR AF: 0.241

Gnomad4 ASJ AF: 0.281

Gnomad4 EAS AF: 0.190

Gnomad4 SAS AF: 0.223

Gnomad4 FIN AF: 0.395

Gnomad4 NFE AF: 0.330

Gnomad4 OTH AF: 0.276

Alfa AF: 0.317 Hom.: 968

Bravo AF: 0.280

Asia WGS AF: 0.199 AC: 692 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 23, 2018

- -

Computational scores

Source: dbNSFP v4.3

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: rs59029193; hg19: chr4-169432466; COSMIC: COSV54990853; COSMIC: COSV54990853;