Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2BP4_ModerateBP6_ModerateBP7

The ENST00000507735.6(PALLD):c.501C>A(p.Pro167Pro) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000748 in 1,337,288 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★). Synonymous variant affecting the same amino acid position (i.e. P167P) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 7.5e-7 ( 0 hom. )

Consequence

PALLD
ENST00000507735.6 splice_region, synonymous

Scores

Splicing: ADA: 0.0001649

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.186

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:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.32).

BP6

Variant 4-168878392-C-A is Benign according to our data. Variant chr4-168878392-C-A is described in ClinVar as Likely_benign. ClinVar VariationId is 4130412.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=0.186 with no splicing effect.

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.1965-12530C>A		intron	N/A	NP_001159580.1
PALLD	NM_001166110.2		c.501C>A	p.Pro167Pro	splice_region synonymous	Exon 2 of 12	NP_001159582.1
PALLD	NM_016081.4		c.1965-12530C>A		intron	N/A	NP_057165.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
PALLD	ENST00000507735.6	TSL:1	c.501C>A	p.Pro167Pro	splice_region synonymous	Exon 2 of 12	ENSP00000424016.1
PALLD	ENST00000505667.6	TSL:1 MANE Select	c.1965-12530C>A		intron	N/A	ENSP00000425556.1
PALLD	ENST00000261509.10	TSL:1	c.1965-12530C>A		intron	N/A	ENSP00000261509.6

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.48e-7

AC:

AN:

1337288

Hom.:

Cov.:

AF XY:

0.00000152

AC XY:

AN XY:

657262

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

28876

American (AMR)

AF:

0.00

AC:

AN:

29176

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

22994

East Asian (EAS)

AF:

0.00

AC:

AN:

33318

South Asian (SAS)

AF:

0.00

AC:

AN:

73312

European-Finnish (FIN)

AF:

0.00

AC:

AN:

32416

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3932

European-Non Finnish (NFE)

AF:

9.46e-7

AC:

AN:

1057628

Other (OTH)

AF:

0.00

AC:

AN:

55636

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions as Germline

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.32

CADD

Benign

(source)

DANN

Benign

0.92

PhyloP100

0.19

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00016

dbscSNV1_RF

Benign

0.0020

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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ENST00000507735.6:c.501C>A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over