Genetic Variant ENST00000507735.6:c.273G>A (chr4-168878164-G-A) – ACMG Classification: Likely_benign (-5 pts)

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7

The ENST00000507735.6(PALLD):c.273G>A(p.Pro91Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000975 in 410,456 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Synonymous variant affecting the same amino acid position (i.e. P91P) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 30)

Exomes 𝑓: 0.0000097 ( 0 hom. )

Consequence

PALLD
ENST00000507735.6 synonymous

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.600

Publications

1 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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new If you want to explore the variant's impact on the transcript ENST00000507735.6, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -5 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.62).

BP6

Variant 4-168878164-G-A is Benign according to our data. Variant chr4-168878164-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 3885244.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.6 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	UniProt
PALLD	NM_001166108.2	MANE Select	c.1965-12758G>A		intron	N/A	NP_001159580.1	Q8WX93-9
PALLD	NM_001166110.2		c.273G>A	p.Pro91Pro	synonymous	Exon 2 of 12	NP_001159582.1	Q8WX93-4
PALLD	NM_016081.4		c.1965-12758G>A		intron	N/A	NP_057165.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PALLD	ENST00000507735.6	TSL:1	c.273G>A	p.Pro91Pro	synonymous	Exon 2 of 12	ENSP00000424016.1	Q8WX93-4
PALLD	ENST00000505667.6	TSL:1 MANE Select	c.1965-12758G>A		intron	N/A	ENSP00000425556.1	Q8WX93-9
PALLD	ENST00000261509.10	TSL:1	c.1965-12758G>A		intron	N/A	ENSP00000261509.6	Q8WX93-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000349

AC:

AN:

57246

AF XY:

0.0000289

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:

0.0000431

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000975

AC:

AN:

410456

Hom.:

Cov.:

AF XY:

0.00000972

AC XY:

AN XY:

205728

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

8150

American (AMR)

AF:

0.00

AC:

AN:

10054

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

7896

East Asian (EAS)

AF:

0.00

AC:

AN:

3744

South Asian (SAS)

AF:

0.0000573

AC:

AN:

34904

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6256

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1186

European-Non Finnish (NFE)

AF:

0.00000620

AC:

AN:

322728

Other (OTH)

AF:

0.00

AC:

AN:

15538

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.463

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Pancreatic adenocarcinoma (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.62

CADD

Benign

7.9

(source)

DANN

Benign

0.91

PhyloP100

-0.60

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over