rs1751992534

Variant names:

• chr4-168877905-C-T
• rs1751992534
• ENST00000507735.6:c.14C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001166110.2(PALLD):​c.14C>T​(p.Ala5Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000151 in 1,325,402 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/18 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. A5T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000015 (0 hom.)
• Consequence: PALLD NM_001166110.2 missense
• Clinical Significance: Uncertain significance criteria provided, multiple submitters, no conflicts U:2
• Conservation: PhyloP100: 2.85
• Publications: 0 publications found

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]

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.18295106).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001166110.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PALLD	NM_001166108.2	MANE Select	c.1965-13017C>T		intron	N/A	NP_001159580.1	Q8WX93-9
	PALLD	NM_001166110.2		c.14C>T	p.Ala5Val	missense	Exon 2 of 12	NP_001159582.1	Q8WX93-4
	PALLD	NM_016081.4		c.1965-13017C>T		intron	N/A	NP_057165.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PALLD	ENST00000507735.6	TSL:1	c.14C>T	p.Ala5Val	missense	Exon 2 of 12	ENSP00000424016.1	Q8WX93-4
	PALLD	ENST00000505667.6	TSL:1 MANE Select	c.1965-13017C>T		intron	N/A	ENSP00000425556.1	Q8WX93-9
	PALLD	ENST00000261509.10	TSL:1	c.1965-13017C>T		intron	N/A	ENSP00000261509.6	Q8WX93-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000151 AC: 2 AN: 1325402 Hom.: 0 Cov.: 31 AF XY: 0.00000153 AC XY: 1 AN XY: 653718

African (AFR) AF: 0.00 AC: 0 AN: 26874

American (AMR) AF: 0.00 AC: 0 AN: 28822

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23336

East Asian (EAS) AF: 0.0000702 AC: 2 AN: 28492

South Asian (SAS) AF: 0.00 AC: 0 AN: 74188

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 32862

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5056

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1050844

Other (OTH) AF: 0.00 AC: 0 AN: 54928

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)
-	1	-	Pancreatic adenocarcinoma (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.26
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	20
DANN	Uncertain	0.99
Eigen	Benign	-0.21
Eigen_PC	Benign	-0.29
FATHMM_MKL	Benign	0.61	D
LIST_S2	Benign	0.54	T
M_CAP	Uncertain	0.22	D
MetaRNN	Benign	0.18	T
MetaSVM	Benign	-0.91	T
PhyloP100		2.9
PROVEAN	Benign	-0.51	N
REVEL	Benign	0.066
Sift	Benign	0.13	T
Sift4G	Benign	0.29	T
Vest4		0.057
MutPred		0.27		Gain of glycosylation at S2 (P = 0.0199)
MVP		0.59
ClinPred		0.21	T
GERP RS		3.0
Mutation Taster		=89/11	polymorphism

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

Other links and lift over

dbSNP: rs1751992534; hg19: chr4-169799056;