4-168512182-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001166108.2(PALLD):c.678C>T(p.Asp226Asp) 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:7

Conservation

PhyloP100: -0.850

Publications

10 publications found

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:

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:

LOC107986198 (HGNC:):

LOC107986198 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001166108.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PALLD	NM_001166108.2	MANE Select	c.678C>T	p.Asp226Asp	synonymous	Exon 2 of 22	NP_001159580.1	Q8WX93-9
	PALLD	NM_016081.4		c.678C>T	p.Asp226Asp	synonymous	Exon 2 of 21	NP_057165.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PALLD	ENST00000505667.6	TSL:1 MANE Select	c.678C>T	p.Asp226Asp	synonymous	Exon 2 of 22	ENSP00000425556.1	Q8WX93-9
PALLD	ENST00000261509.10	TSL:1	c.678C>T	p.Asp226Asp	synonymous	Exon 2 of 21	ENSP00000261509.6	Q8WX93-2
PALLD	ENST00000968439.1		c.678C>T	p.Asp226Asp	synonymous	Exon 2 of 22	ENSP00000638498.1

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

GnomAD2 exomes

AF:

0.281

AC:

70264

AN:

250422

AF XY:

0.282

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 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

African (AFR)

AF:

0.244

AC:

8151

AN:

33434

American (AMR)

AF:

0.188

AC:

8404

AN:

44690

Ashkenazi Jewish (ASJ)

AF:

0.298

AC:

7778

AN:

26126

East Asian (EAS)

AF:

0.194

AC:

7701

AN:

39694

South Asian (SAS)

AF:

0.225

AC:

19404

AN:

86248

European-Finnish (FIN)

AF:

0.393

AC:

20989

AN:

53394

Middle Eastern (MID)

AF:

0.239

AC:

1375

AN:

5762

European-Non Finnish (NFE)

AF:

0.326

AC:

362244

AN:

1111516

Other (OTH)

AF:

0.297

AC:

17929

AN:

60364

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.470

Heterozygous variant carriers

18848

37695

56543

75390

94238

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

11530

23060

34590

46120

57650

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.293

AC:

44471

AN:

151782

Hom.:

6563

Cov.:

AF XY:

0.292

AC XY:

21622

AN XY:

74140

show subpopulations

African (AFR)

AF:

0.246

AC:

10214

AN:

41440

American (AMR)

AF:

0.241

AC:

3683

AN:

15260

Ashkenazi Jewish (ASJ)

AF:

0.281

AC:

973

AN:

3466

East Asian (EAS)

AF:

0.192

AC:

988

AN:

5156

South Asian (SAS)

AF:

0.219

AC:

1053

AN:

4816

European-Finnish (FIN)

AF:

0.395

AC:

4159

AN:

10540

Middle Eastern (MID)

AF:

0.284

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.330

AC:

22388

AN:

67804

Other (OTH)

AF:

0.276

AC:

582

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1591

3183

4774

6366

7957

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

436

872

1308

1744

2180

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.307

Hom.:

23326

Bravo

AF:

0.280

Asia WGS

AF:

0.196

AC:

683

AN:

3478

EpiCase

AF:

0.319

EpiControl

AF:

0.314

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

not specified (2)

Pancreatic cancer, susceptibility to, 1 (2)

Pancreatic adenocarcinoma (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.42

(source)

DANN

Benign

0.28

PhyloP100

-0.85

Mutation Taster

=300/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over