4-168512182-C-T

Position:

chr4-168512182-C-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001166108.2(PALLD):c.678C>T(p.Asp226=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.309 in 1,613,010 control chromosomes in the GnomAD database, including 78,940 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.29 ( 6563 hom., cov: 32)

Exomes 𝑓: 0.31 ( 72377 hom. )

Consequence

PALLD
NM_001166108.2 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.850

Variant links:

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]

PALLD links:

LOC107986198 (HGNC:):

LOC107986198 links:

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]

DDX60L links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 4-168512182-C-T is Benign according to our data. Variant chr4-168512182-C-T is described in ClinVar as [Benign]. Clinvar id is 348032.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.85 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.327 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PALLD	NM_001166108.2 linkuse as main transcript	c.678C>T	p.Asp226=	synonymous_variant	2/22	ENST00000505667.6
LOC107986198	XR_001741448.3 linkuse as main transcript	n.280+18379G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PALLD	ENST00000505667.6 linkuse as main transcript	c.678C>T	p.Asp226=	synonymous_variant	2/22	1	NM_001166108.2	A2	Q8WX93-9

Frequencies

GnomAD3 genomes

AF:

0.293

AC:

44452

AN:

151662

Hom.:

6558

Cov.:

show subpopulations

Gnomad AFR

AF:

0.246

Gnomad AMI

AF:

0.388

Gnomad AMR

AF:

0.242

Gnomad ASJ

AF:

0.281

Gnomad EAS

AF:

0.191

Gnomad SAS

AF:

0.219

Gnomad FIN

AF:

0.395

Gnomad MID

AF:

0.271

Gnomad NFE

AF:

0.330

Gnomad OTH

AF:

0.280

GnomAD3 exomes

AF:

0.281

AC:

70264

AN:

250422

Hom.:

10518

AF XY:

0.282

AC XY:

38195

AN XY:

135332

show subpopulations

Gnomad AFR exome

AF:

0.246

Gnomad AMR exome

AF:

0.180

Gnomad ASJ exome

AF:

0.297

Gnomad EAS exome

AF:

0.176

Gnomad SAS exome

AF:

0.222

Gnomad FIN exome

AF:

0.399

Gnomad NFE exome

AF:

0.324

Gnomad OTH exome

AF:

0.295

GnomAD4 exome

AF:

0.311

AC:

453975

AN:

1461228

Hom.:

72377

Cov.:

AF XY:

0.309

AC XY:

224312

AN XY:

726902

show subpopulations

Gnomad4 AFR exome

AF:

0.244

Gnomad4 AMR exome

AF:

0.188

Gnomad4 ASJ exome

AF:

0.298

Gnomad4 EAS exome

AF:

0.194

Gnomad4 SAS exome

AF:

0.225

Gnomad4 FIN exome

AF:

0.393

Gnomad4 NFE exome

AF:

0.326

Gnomad4 OTH exome

AF:

0.297

GnomAD4 genome

AF:

0.293

AC:

44471

AN:

151782

Hom.:

6563

Cov.:

AF XY:

0.292

AC XY:

21622

AN XY:

74140

show subpopulations

Gnomad4 AFR

AF:

0.246

Gnomad4 AMR

AF:

0.241

Gnomad4 ASJ

AF:

0.281

Gnomad4 EAS

AF:

0.192

Gnomad4 SAS

AF:

0.219

Gnomad4 FIN

AF:

0.395

Gnomad4 NFE

AF:

0.330

Gnomad4 OTH

AF:

0.276

Alfa

AF:

0.312

Hom.:

14892

Bravo

AF:

0.280

Asia WGS

AF:

0.196

AC:

683

AN:

3478

EpiCase

AF:

0.319

EpiControl

AF:

0.314

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Pancreatic cancer, susceptibility to, 1

Benign:2

Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
Benign, criteria provided, single submitter	clinical testing	KCCC/NGS Laboratory, Kuwait Cancer Control Center	Jul 07, 2023	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 28, 2016

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

Pancreatic adenocarcinoma

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Nov 22, 2022

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 03, 2015

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.42

DANN

Benign

0.28

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over