ENST00000507699.1:n.3498G>A

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000507699.1(PALLD):n.3498G>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.125 in 195,530 control chromosomes in the GnomAD database, including 1,670 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.13 ( 1384 hom., cov: 33)

Exomes 𝑓: 0.11 ( 286 hom. )

Consequence

PALLD
ENST00000507699.1 non_coding_transcript_exon

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 1.95

Publications

11 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:

CBR4 (HGNC:25891): (carbonyl reductase 4) Enables several functions, including 3-oxoacyl-[acyl-carrier-protein] reductase (NADPH) activity; NADPH binding activity; and NADPH dehydrogenase (quinone) activity. Involved in fatty acid biosynthetic process; glycoside metabolic process; and protein tetramerization. Located in mitochondrial matrix. Part of oxidoreductase complex. [provided by Alliance of Genome Resources, Apr 2022]

CBR4 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 4-168928086-G-A is Benign according to our data. Variant chr4-168928086-G-A is described in ClinVar as Benign. ClinVar VariationId is 348067.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.179 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PALLD	NM_001166108.2 link	c.*1906G>A		3_prime_UTR_variant	Exon 22 of 22	ENST00000505667.6	NP_001159580.1	Q8WX93-9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PALLD	ENST00000505667.6 link	c.*1906G>A		3_prime_UTR_variant	Exon 22 of 22	1	NM_001166108.2	ENSP00000425556.1		Q8WX93-9

Frequencies

GnomAD3 genomes

AF:

0.128

AC:

19456

AN:

152022

Hom.:

1384

Cov.:

show subpopulations

Gnomad AFR

AF:

0.182

Gnomad AMI

AF:

0.223

Gnomad AMR

AF:

0.0912

Gnomad ASJ

AF:

0.0965

Gnomad EAS

AF:

0.0728

Gnomad SAS

AF:

0.0789

Gnomad FIN

AF:

0.0757

Gnomad MID

AF:

0.209

Gnomad NFE

AF:

0.119

Gnomad OTH

AF:

0.133

GnomAD4 exome

AF:

0.114

AC:

4926

AN:

43390

Hom.:

286

Cov.:

AF XY:

0.115

AC XY:

2309

AN XY:

20092

show subpopulations

African (AFR)

AF:

0.183

AC:

321

AN:

1750

American (AMR)

AF:

0.0861

AC:

102

AN:

1184

Ashkenazi Jewish (ASJ)

AF:

0.0938

AC:

250

AN:

2666

East Asian (EAS)

AF:

0.0738

AC:

541

AN:

7330

South Asian (SAS)

AF:

0.0513

AC:

AN:

390

European-Finnish (FIN)

AF:

0.0852

AC:

AN:

446

Middle Eastern (MID)

AF:

0.165

AC:

AN:

272

European-Non Finnish (NFE)

AF:

0.125

AC:

3217

AN:

25762

Other (OTH)

AF:

0.109

AC:

392

AN:

3590

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

230

459

689

918

1148

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<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:

0.128

AC:

19472

AN:

152140

Hom.:

1384

Cov.:

AF XY:

0.124

AC XY:

9226

AN XY:

74378

show subpopulations

African (AFR)

AF:

0.182

AC:

7560

AN:

41478

American (AMR)

AF:

0.0911

AC:

1392

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.0965

AC:

335

AN:

3472

East Asian (EAS)

AF:

0.0729

AC:

378

AN:

5182

South Asian (SAS)

AF:

0.0779

AC:

376

AN:

4824

European-Finnish (FIN)

AF:

0.0757

AC:

802

AN:

10588

Middle Eastern (MID)

AF:

0.211

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.119

AC:

8086

AN:

67998

Other (OTH)

AF:

0.132

AC:

278

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

870

1740

2610

3480

4350

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

210

420

630

840

1050

<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:

0.119

Hom.:

832

Bravo

AF:

0.132

Asia WGS

AF:

0.0770

AC:

267

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Mar 03, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Pancreatic cancer, susceptibility to, 1

Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

7.5

(source)

DANN

Benign

0.68

PhyloP100

1.9

Mutation Taster

=100/0

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over