rs551131343

Variant names:

• chr4-168878174-G-C
• rs551131343
• ENST00000507735.6:c.283G>C

Your query was ambiguous. Multiple possible variants found:

• chr4-168878174-G-C
• chr4-168878174-G-T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_001166110.2(PALLD):​c.283G>C​(p.Val95Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000817 in 1,346,272 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/18 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. V95G) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000074 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000082 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PALLD NM_001166110.2 missense
• Clinical Significance: Uncertain significance criteria provided, multiple submitters, no conflicts U:2
• Conservation: PhyloP100: 4.67
• 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: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.05351612).
• BS2: High AC in GnomAdExome4 at 11 AD gene.

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.1965-12748G>C		intron	N/A	NP_001159580.1
	PALLD	NM_001166110.2		c.283G>C	p.Val95Leu	missense	Exon 2 of 12	NP_001159582.1
	PALLD	NM_016081.4		c.1965-12748G>C		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.283G>C	p.Val95Leu	missense	Exon 2 of 12	ENSP00000424016.1
	PALLD	ENST00000505667.6	TSL:1 MANE Select	c.1965-12748G>C		intron	N/A	ENSP00000425556.1
	PALLD	ENST00000261509.10	TSL:1	c.1965-12748G>C		intron	N/A	ENSP00000261509.6

Frequencies

GnomAD3 genomes AF: 0.0000737 AC: 11 AN: 149158 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000282

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000101 AC: 1 AN: 98756 AF XY: 0.0000181

Gnomad AFR exome AF: 0.000600

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: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000817 AC: 11 AN: 1346272 Hom.: 0 Cov.: 42 AF XY: 0.00000753 AC XY: 5 AN XY: 664068

African (AFR) AF: 0.000378 AC: 10 AN: 26438

American (AMR) AF: 0.00 AC: 0 AN: 31904

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23942

East Asian (EAS) AF: 0.00 AC: 0 AN: 31556

South Asian (SAS) AF: 0.00 AC: 0 AN: 75582

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33266

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4076

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1063564

Other (OTH) AF: 0.0000179 AC: 1 AN: 55944

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000737 AC: 11 AN: 149264 Hom.: 0 Cov.: 32 AF XY: 0.0000548 AC XY: 4 AN XY: 73000

African (AFR) AF: 0.000281 AC: 11 AN: 39106

American (AMR) AF: 0.00 AC: 0 AN: 15142

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5096

South Asian (SAS) AF: 0.00 AC: 0 AN: 4802

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10534

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 284

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67824

Other (OTH) AF: 0.00 AC: 0 AN: 2096

Alfa AF: 0.0000843 Hom.: 0

ClinVar

ClinVar submissions as Germline

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	0.20
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	14
DANN	Benign	0.55
Eigen	Benign	-0.56
Eigen_PC	Benign	-0.52
FATHMM_MKL	Uncertain	0.80	D
LIST_S2	Benign	0.77	T
M_CAP	Benign	0.046	D
MetaRNN	Benign	0.054	T
MetaSVM	Benign	-1.0	T
PhyloP100		4.7
PROVEAN	Benign	-0.070	N
REVEL	Benign	0.067
Sift	Benign	0.47	T
Sift4G	Benign	1.0	T
Vest4		0.11
MVP		0.52
ClinPred		0.037	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: rs551131343; hg19: chr4-169799325;