ENST00000507735.6:c.415C>T

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4BP6BS2

The ENST00000507735.6(PALLD):c.415C>T(p.Pro139Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0008 in 1,527,100 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. P139P) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.00024 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00086 ( 4 hom. )

Consequence

PALLD
ENST00000507735.6 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:2B:2O:1

Conservation

PhyloP100: 5.40

Publications

4 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.34723958).

BP6

Variant 4-168878306-C-T is Benign according to our data. Variant chr4-168878306-C-T is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 2572.

BS2

High AC in GnomAd4 at 37 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000507735.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PALLD	NM_001166108.2	MANE Select	c.1965-12616C>T		intron	N/A	NP_001159580.1	Q8WX93-9
PALLD	NM_001166110.2		c.415C>T	p.Pro139Ser	missense	Exon 2 of 12	NP_001159582.1	Q8WX93-4
PALLD	NM_016081.4		c.1965-12616C>T		intron	N/A	NP_057165.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PALLD	ENST00000507735.6	TSL:1	c.415C>T	p.Pro139Ser	missense	Exon 2 of 12	ENSP00000424016.1	Q8WX93-4
PALLD	ENST00000505667.6	TSL:1 MANE Select	c.1965-12616C>T		intron	N/A	ENSP00000425556.1	Q8WX93-9
PALLD	ENST00000261509.10	TSL:1	c.1965-12616C>T		intron	N/A	ENSP00000261509.6	Q8WX93-2

Frequencies

GnomAD3 genomes

AF:

0.000243

AC:

AN:

152194

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000965

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000470

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000205

AC:

AN:

122174

AF XY:

0.000239

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000486

Gnomad OTH exome

AF:

0.000531

GnomAD4 exome

AF:

0.000862

AC:

1185

AN:

1374906

Hom.:

Cov.:

AF XY:

0.000843

AC XY:

572

AN XY:

678180

show subpopulations

African (AFR)

AF:

0.000163

AC:

AN:

30682

American (AMR)

AF:

0.00

AC:

AN:

35198

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24926

East Asian (EAS)

AF:

0.00

AC:

AN:

35032

South Asian (SAS)

AF:

0.0000512

AC:

AN:

78192

European-Finnish (FIN)

AF:

0.00

AC:

AN:

33428

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4216

European-Non Finnish (NFE)

AF:

0.00107

AC:

1151

AN:

1075810

Other (OTH)

AF:

0.000435

AC:

AN:

57422

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

128

193

257

321

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

150

200

250

<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:

0.000243

AC:

AN:

152194

Hom.:

Cov.:

AF XY:

0.000134

AC XY:

AN XY:

74352

show subpopulations

African (AFR)

AF:

0.0000965

AC:

AN:

41464

American (AMR)

AF:

0.0000654

AC:

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5174

South Asian (SAS)

AF:

0.00

AC:

AN:

4836

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.000470

AC:

AN:

68026

Other (OTH)

AF:

0.00

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.520

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.000299

Hom.:

Bravo

AF:

0.000249

ExAC

AF:

0.0000607

AC:

ClinVar

ClinVar submissions

Significance:Conflicting classifications of pathogenicity

Revision:criteria provided, conflicting classifications

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (2)

PALLD-related disorder (1)

Pancreatic adenocarcinoma (1)

Pancreatic cancer, susceptibility to, 1 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.090

BayesDel_noAF

Uncertain

-0.030

CADD

Benign

(source)

DANN

Uncertain

1.0

Eigen

Uncertain

0.45

Eigen_PC

Uncertain

0.37

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.77

M_CAP

Uncertain

0.22

MetaRNN

Benign

0.35

MetaSVM

Uncertain

0.53

PhyloP100

5.4

PROVEAN

Uncertain

-3.4

REVEL

Uncertain

0.45

Sift

Uncertain

0.0050

Sift4G

Uncertain

0.012

Vest4

0.38

MVP

0.70

ClinPred

0.21

GERP RS

4.6

Mutation Taster

=22/78

disease causing

(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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over