chr4-168878257-G-C

Position:

chr4-168878257-G-C

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_001166110.2(PALLD):c.366G>C(p.Gln122His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000819 in 1,524,610 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/15 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0012 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00077 ( 7 hom. )

Consequence

PALLD
NM_001166110.2 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.114

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 made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0038834214).

BP6

Variant 4-168878257-G-C is Benign according to our data. Variant chr4-168878257-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 136005.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 186 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PALLD	NM_001166108.2 link	c.1965-12665G>C		intron_variant		ENST00000505667.6	NP_001159580.1	Q8WX93-9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PALLD	ENST00000505667.6 link	c.1965-12665G>C		intron_variant		1	NM_001166108.2	ENSP00000425556.1		Q8WX93-9

Frequencies

GnomAD3 genomes

AF:

0.00121

AC:

184

AN:

151878

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00485

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.000194

Gnomad SAS

AF:

0.00125

Gnomad FIN

AF:

0.00388

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000750

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.00261

AC:

314

AN:

120220

Hom.:

AF XY:

0.00197

AC XY:

130

AN XY:

66134

show subpopulations

Gnomad AFR exome

AF:

0.000217

Gnomad AMR exome

AF:

0.0105

Gnomad ASJ exome

AF:

0.000514

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000473

Gnomad FIN exome

AF:

0.00412

Gnomad NFE exome

AF:

0.000535

Gnomad OTH exome

AF:

0.00162

GnomAD4 exome

AF:

0.000774

AC:

1063

AN:

1372626

Hom.:

Cov.:

AF XY:

0.000753

AC XY:

510

AN XY:

677194

show subpopulations

Gnomad4 AFR exome

AF:

0.0000662

Gnomad4 AMR exome

AF:

0.0107

Gnomad4 ASJ exome

AF:

0.000484

Gnomad4 EAS exome

AF:

0.000231

Gnomad4 SAS exome

AF:

0.000732

Gnomad4 FIN exome

AF:

0.00577

Gnomad4 NFE exome

AF:

0.000328

Gnomad4 OTH exome

AF:

0.00108

GnomAD4 genome

AF:

0.00122

AC:

186

AN:

151984

Hom.:

Cov.:

AF XY:

0.00112

AC XY:

AN XY:

74306

show subpopulations

Gnomad4 AFR

AF:

0.000121

Gnomad4 AMR

AF:

0.00497

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.000195

Gnomad4 SAS

AF:

0.00125

Gnomad4 FIN

AF:

0.00388

Gnomad4 NFE

AF:

0.000751

Gnomad4 OTH

AF:

0.00237

Alfa

AF:

0.00136

Hom.:

Bravo

AF:

0.00146

ExAC

AF:

0.000531

AC:

Asia WGS

AF:

0.00145

AC:

AN:

3468

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	May 13, 2020	- -
Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Jun 01, 2022	PALLD: BS1, BS2 -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 29, 2024

This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Pancreatic adenocarcinoma

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 23, 2025

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.51

CADD

Benign

0.83

DANN

Benign

0.58

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.023

LIST_S2

Benign

0.41

M_CAP

Benign

0.014

MetaRNN

Benign

0.0039

MetaSVM

Benign

-1.0

PROVEAN

Benign

-0.58

REVEL

Benign

0.041

Sift

Benign

0.034

Sift4G

Benign

0.27

Vest4

0.067

MVP

0.17

ClinPred

0.0021

GERP RS

0.15

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over