ENST00000507735.6:c.276A>C

Variant names:

• chr4-168878167-A-C
• rs863224385
• ENST00000507735.6:c.276A>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.276A>C​(p.Pro92Pro) 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 Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0018 (0 hom., cov: 29)
  • Exomes 𝑓: 0.0079 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PALLD ENST00000507735.6 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.780
• 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=-0.62).
• BP6: Variant 4-168878167-A-C is Benign according to our data. Variant chr4-168878167-A-C is described in ClinVar as Benign. ClinVar VariationId is 215806.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.78 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.1965-12755A>C		intron	N/A	NP_001159580.1	Q8WX93-9
	PALLD	NM_001166110.2		c.276A>C	p.Pro92Pro	synonymous	Exon 2 of 12	NP_001159582.1	Q8WX93-4
	PALLD	NM_016081.4		c.1965-12755A>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.276A>C	p.Pro92Pro	synonymous	Exon 2 of 12	ENSP00000424016.1	Q8WX93-4
	PALLD	ENST00000505667.6	TSL:1 MANE Select	c.1965-12755A>C		intron	N/A	ENSP00000425556.1	Q8WX93-9
	PALLD	ENST00000261509.10	TSL:1	c.1965-12755A>C		intron	N/A	ENSP00000261509.6	Q8WX93-2

Frequencies

GnomAD3 genomes AF: 0.00181 AC: 169 AN: 93584 Hom.: 0 Cov.: 29

Gnomad AFR AF: 0.00339

Gnomad AMI AF: 0.00190

Gnomad AMR AF: 0.00103

Gnomad ASJ AF: 0.000411

Gnomad EAS AF: 0.000613

Gnomad SAS AF: 0.00197

Gnomad FIN AF: 0.00361

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00113

Gnomad OTH AF: 0.00153

GnomAD2 exomes AF: 0.00914 AC: 621 AN: 67926 AF XY: 0.00721

Gnomad AFR exome AF: 0.0546

Gnomad AMR exome AF: 0.0299

Gnomad ASJ exome AF: 0.00727

Gnomad EAS exome AF: 0.00697

Gnomad FIN exome AF: 0.00681

Gnomad NFE exome AF: 0.00576

Gnomad OTH exome AF: 0.00580

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00787 AC: 5710 AN: 725918 Hom.: 0 Cov.: 36 AF XY: 0.00781 AC XY: 2806 AN XY: 359264

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

African (AFR) AF: 0.0131 AC: 174 AN: 13238

American (AMR) AF: 0.0426 AC: 603 AN: 14166

Ashkenazi Jewish (ASJ) AF: 0.0123 AC: 131 AN: 10686

East Asian (EAS) AF: 0.00529 AC: 35 AN: 6620

South Asian (SAS) AF: 0.0137 AC: 684 AN: 49852

European-Finnish (FIN) AF: 0.0212 AC: 167 AN: 7876

Middle Eastern (MID) AF: 0.0146 AC: 27 AN: 1850

European-Non Finnish (NFE) AF: 0.00602 AC: 3585 AN: 595374

Other (OTH) AF: 0.0116 AC: 304 AN: 26256

⚠️ 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: 0.00181 AC: 169 AN: 93620 Hom.: 0 Cov.: 29 AF XY: 0.00164 AC XY: 75 AN XY: 45738

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

African (AFR) AF: 0.00338 AC: 79 AN: 23366

American (AMR) AF: 0.00102 AC: 10 AN: 9770

Ashkenazi Jewish (ASJ) AF: 0.000411 AC: 1 AN: 2432

East Asian (EAS) AF: 0.000614 AC: 2 AN: 3258

South Asian (SAS) AF: 0.00197 AC: 5 AN: 2536

European-Finnish (FIN) AF: 0.00361 AC: 18 AN: 4986

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 222

European-Non Finnish (NFE) AF: 0.00113 AC: 51 AN: 45208

Other (OTH) AF: 0.00152 AC: 2 AN: 1316

⚠️ 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: 0.0482 Hom.: 0

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	PALLD-related disorder (1)
-	-	1	Pancreatic adenocarcinoma (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.62
CADD	Benign	8.7
DANN	Benign	0.43
PhyloP100		0.78
Mutation Taster		=98/2	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: rs863224385; hg19: chr4-169799318;