ENST00000507735.6:c.1891C>T

Variant names:

• chr4-168926257-C-T
• rs1060502976
• ENST00000507735.6:c.1891C>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The ENST00000507735.6(PALLD):​c.1891C>T​(p.Arg631Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000013 in 1,383,968 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. R631Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.000013 (0 hom.)
• Consequence: PALLD ENST00000507735.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.16
• Publications: 2 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: Likely_benign. The variant received -4 ACMG points.

• BS2: High AC in GnomAdExome4 at 18 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PALLD	NM_001166108.2	MANE Select	c.*77C>T		3_prime_UTR	Exon 22 of 22	NP_001159580.1
	PALLD	NM_001166109.2		c.2206C>T	p.Arg736Trp	missense	Exon 19 of 19	NP_001159581.1
	PALLD	NM_001166110.2		c.1891C>T	p.Arg631Trp	missense	Exon 12 of 12	NP_001159582.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PALLD	ENST00000507735.6	TSL:1	c.1891C>T	p.Arg631Trp	missense	Exon 12 of 12	ENSP00000424016.1
	PALLD	ENST00000505667.6	TSL:1 MANE Select	c.*77C>T		3_prime_UTR	Exon 22 of 22	ENSP00000425556.1
	PALLD	ENST00000261509.10	TSL:1	c.*77C>T		3_prime_UTR	Exon 21 of 21	ENSP00000261509.6

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000696 AC: 1 AN: 143636 AF XY: 0.0000130

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000409

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: 0.0000130 AC: 18 AN: 1383968 Hom.: 0 Cov.: 31 AF XY: 0.00000732 AC XY: 5 AN XY: 682880

African (AFR) AF: 0.00 AC: 0 AN: 31560

American (AMR) AF: 0.0000281 AC: 1 AN: 35640

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25160

East Asian (EAS) AF: 0.00 AC: 0 AN: 35714

South Asian (SAS) AF: 0.0000379 AC: 3 AN: 79072

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 34974

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5686

European-Non Finnish (NFE) AF: 0.0000102 AC: 11 AN: 1078288

Other (OTH) AF: 0.0000518 AC: 3 AN: 57874

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Pancreatic adenocarcinoma (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.34
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	0.060
CADD	Benign	19
DANN	Pathogenic	1.0
Eigen	Pathogenic	0.74
Eigen_PC	Pathogenic	0.73
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Uncertain	0.96	D
M_CAP	Uncertain	0.13	D
MetaRNN	Uncertain	0.49	T
MetaSVM	Uncertain	-0.13	T
PhyloP100		3.2
PROVEAN	Pathogenic	-4.8	D
REVEL	Uncertain	0.37
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.0020	D
Vest4		0.54
MVP		0.74
ClinPred		0.62	D
GERP RS		6.0
Mutation Taster		=57/43	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: rs1060502976; hg19: chr4-169847408; COSMIC: COSV54995950; COSMIC: COSV54995950;