chr4-168497248-TA-T

Position:

• chr4-168497248-TA-T

Variant summary

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

The NM_001166108.2(PALLD):​c.-83+67del variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.44 (14003 hom., cov: 0)
  • Failed GnomAD Quality Control
• Consequence: PALLD NM_001166108.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.807

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 4-168497248-TA-T is Benign according to our data. Variant chr4-168497248-TA-T is described in ClinVar as [Benign]. Clinvar id is 1245061.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.619 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PALLD	NM_001166108.2	c.-83+67del		intron_variant		ENST00000505667.6
LOC107986198	XR_001741448.3	n.281-4364del		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PALLD	ENST00000505667.6	c.-83+67del		intron_variant		1	NM_001166108.2	A2

Frequencies

GnomAD3 genomes AF: 0.439 AC: 64491 AN: 147060 Hom.: 13991 Cov.: 0

Gnomad AFR AF: 0.452

Gnomad AMI AF: 0.558

Gnomad AMR AF: 0.536

Gnomad ASJ AF: 0.381

Gnomad EAS AF: 0.637

Gnomad SAS AF: 0.351

Gnomad FIN AF: 0.466

Gnomad MID AF: 0.397

Gnomad NFE AF: 0.398

Gnomad OTH AF: 0.437

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

GnomAD4 genome AF: 0.439 AC: 64542 AN: 147124 Hom.: 14003 Cov.: 0 AF XY: 0.443 AC XY: 31719 AN XY: 71542

Gnomad4 AFR AF: 0.452

Gnomad4 AMR AF: 0.536

Gnomad4 ASJ AF: 0.381

Gnomad4 EAS AF: 0.637

Gnomad4 SAS AF: 0.351

Gnomad4 FIN AF: 0.466

Gnomad4 NFE AF: 0.398

Gnomad4 OTH AF: 0.440

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

Aug 30, 2019

- -

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: rs34221810; hg19: chr4-169418399;