4-168878174-G-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The ENST00000507735.6(PALLD):c.283G>C(p.Val95Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000817 in 1,346,272 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V95G) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000074 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000082 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

PALLD
ENST00000507735.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:2

Conservation

PhyloP100: 4.67

Publications

0 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: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.05351612).

BS2

High AC in GnomAdExome4 at 11 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
PALLD	NM_001166108.2	MANE Select	c.1965-12748G>C		intron	N/A	NP_001159580.1
PALLD	NM_001166110.2		c.283G>C	p.Val95Leu	missense	Exon 2 of 12	NP_001159582.1
PALLD	NM_016081.4		c.1965-12748G>C		intron	N/A	NP_057165.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
PALLD	ENST00000507735.6	TSL:1	c.283G>C	p.Val95Leu	missense	Exon 2 of 12	ENSP00000424016.1
PALLD	ENST00000505667.6	TSL:1 MANE Select	c.1965-12748G>C		intron	N/A	ENSP00000425556.1
PALLD	ENST00000261509.10	TSL:1	c.1965-12748G>C		intron	N/A	ENSP00000261509.6

Frequencies

GnomAD3 genomes

AF:

0.0000737

AC:

AN:

149158

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000282

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000101

AC:

AN:

98756

AF XY:

0.0000181

show subpopulations

Gnomad AFR exome

AF:

0.000600

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000817

AC:

AN:

1346272

Hom.:

Cov.:

AF XY:

0.00000753

AC XY:

AN XY:

664068

show subpopulations

African (AFR)

AF:

0.000378

AC:

AN:

26438

American (AMR)

AF:

0.00

AC:

AN:

31904

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23942

East Asian (EAS)

AF:

0.00

AC:

AN:

31556

South Asian (SAS)

AF:

0.00

AC:

AN:

75582

European-Finnish (FIN)

AF:

0.00

AC:

AN:

33266

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4076

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1063564

Other (OTH)

AF:

0.0000179

AC:

AN:

55944

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.402

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000737

AC:

AN:

149264

Hom.:

Cov.:

AF XY:

0.0000548

AC XY:

AN XY:

73000

show subpopulations

African (AFR)

AF:

0.000281

AC:

AN:

39106

American (AMR)

AF:

0.00

AC:

AN:

15142

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5096

South Asian (SAS)

AF:

0.00

AC:

AN:

4802

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10534

Middle Eastern (MID)

AF:

0.00

AC:

AN:

284

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67824

Other (OTH)

AF:

0.00

AC:

AN:

2096

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.448

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:

0.0000843

Hom.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Aug 08, 2025

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.283G>C (p.V95L) alteration is located in exon 2 (coding exon 1) of the PALLD gene. This alteration results from a G to C substitution at nucleotide position 283, causing the valine (V) at amino acid position 95 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

Pancreatic adenocarcinoma

Uncertain:1

Jan 23, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This sequence change replaces valine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 95 of the PALLD protein (p.Val95Leu). This variant is present in population databases (rs551131343, gnomAD 0.03%). This variant has not been reported in the literature in individuals affected with PALLD-related conditions. ClinVar contains an entry for this variant (Variation ID: 238609). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant¬†is likely to be tolerated. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.20

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.44

CADD

Benign

(source)

DANN

Benign

0.55

Eigen

Benign

-0.56

Eigen_PC

Benign

-0.52

FATHMM_MKL

Uncertain

0.80

LIST_S2

Benign

0.77

M_CAP

Benign

0.046

MetaRNN

Benign

0.054

MetaSVM

Benign

-1.0

PhyloP100

4.7

PROVEAN

Benign

-0.070

REVEL

Benign

0.067

Sift

Benign

0.47

Sift4G

Benign

1.0

Vest4

0.11

MVP

0.52

ClinPred

0.037

GERP RS

3.0

Mutation Taster

=89/11

polymorphism

(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

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over