ENST00000507735.6:c.273G>C

Variant names:

• chr4-168878164-G-C
• rs777359545
• ENST00000507735.6:c.273G>C

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP6_Very_Strong BP7

The ENST00000507735.6(PALLD):​c.273G>C​(p.Pro91Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. 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: 𝑓 0.0016 (0 hom., cov: 30)
  • Exomes 𝑓: 0.028 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PALLD ENST00000507735.6 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -0.600
• Publications: 1 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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.64).
• BP6: Variant 4-168878164-G-C is Benign according to our data. Variant chr4-168878164-G-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 215805.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PALLD	NM_001166108.2	MANE Select	c.1965-12758G>C		intron	N/A	NP_001159580.1	Q8WX93-9
	PALLD	NM_001166110.2		c.273G>C	p.Pro91Pro	synonymous	Exon 2 of 12	NP_001159582.1	Q8WX93-4
	PALLD	NM_016081.4		c.1965-12758G>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.273G>C	p.Pro91Pro	synonymous	Exon 2 of 12	ENSP00000424016.1	Q8WX93-4
	PALLD	ENST00000505667.6	TSL:1 MANE Select	c.1965-12758G>C		intron	N/A	ENSP00000425556.1	Q8WX93-9
	PALLD	ENST00000261509.10	TSL:1	c.1965-12758G>C		intron	N/A	ENSP00000261509.6	Q8WX93-2

Frequencies

GnomAD3 genomes AF: 0.00156 AC: 161 AN: 102898 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.00299

Gnomad AMI AF: 0.00179

Gnomad AMR AF: 0.00124

Gnomad ASJ AF: 0.000379

Gnomad EAS AF: 0.00175

Gnomad SAS AF: 0.00171

Gnomad FIN AF: 0.00415

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000644

Gnomad OTH AF: 0.00147

GnomAD2 exomes AF: 0.0208 AC: 1188 AN: 57246 AF XY: 0.0161

Gnomad AFR exome AF: 0.112

Gnomad AMR exome AF: 0.0803

Gnomad ASJ exome AF: 0.0196

Gnomad EAS exome AF: 0.0283

Gnomad FIN exome AF: 0.0132

Gnomad NFE exome AF: 0.0110

Gnomad OTH exome AF: 0.0211

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0280 AC: 10284 AN: 367294 Hom.: 0 Cov.: 25 AF XY: 0.0270 AC XY: 4998 AN XY: 185078

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0451 AC: 323 AN: 7168

American (AMR) AF: 0.131 AC: 1123 AN: 8602

Ashkenazi Jewish (ASJ) AF: 0.0401 AC: 288 AN: 7176

East Asian (EAS) AF: 0.0274 AC: 88 AN: 3216

South Asian (SAS) AF: 0.0277 AC: 895 AN: 32364

European-Finnish (FIN) AF: 0.0486 AC: 265 AN: 5454

Middle Eastern (MID) AF: 0.0372 AC: 39 AN: 1048

European-Non Finnish (NFE) AF: 0.0235 AC: 6769 AN: 288510

Other (OTH) AF: 0.0359 AC: 494 AN: 13756

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00155 AC: 160 AN: 102930 Hom.: 0 Cov.: 30 AF XY: 0.00139 AC XY: 70 AN XY: 50308

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00299 AC: 78 AN: 26100

American (AMR) AF: 0.00124 AC: 13 AN: 10460

Ashkenazi Jewish (ASJ) AF: 0.000379 AC: 1 AN: 2636

East Asian (EAS) AF: 0.00175 AC: 6 AN: 3420

South Asian (SAS) AF: 0.00171 AC: 5 AN: 2918

European-Finnish (FIN) AF: 0.00415 AC: 23 AN: 5536

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 232

European-Non Finnish (NFE) AF: 0.000624 AC: 31 AN: 49696

Other (OTH) AF: 0.00146 AC: 2 AN: 1372

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.0102 Hom.: 0

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not specified (3)
-	-	1	not provided (1)
-	-	1	Pancreatic adenocarcinoma (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	7.1
DANN	Benign	0.68
PhyloP100		-0.60
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: rs777359545; hg19: chr4-169799315;