rs114593924

Variant names:

• chr4-168925017-T-C
• rs114593924
• NM_001166108.2:c.3297T>C

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP6_Very_Strong BP7 BS2

The NM_001166108.2(PALLD):​c.3297T>C​(p.Tyr1099Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00303 in 1,614,102 control chromosomes in the GnomAD database, including 97 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0053 (12 hom., cov: 32)
  • Exomes 𝑓: 0.0028 (85 hom.)
• Consequence: PALLD NM_001166108.2 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -0.390
• Publications: 4 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.

• BP6: Variant 4-168925017-T-C is Benign according to our data. Variant chr4-168925017-T-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 136000.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.39 with no splicing effect.
• BS2: High AC in GnomAd4 at 811 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001166108.2. 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.3297T>C	p.Tyr1099Tyr	synonymous	Exon 20 of 22	NP_001159580.1	Q8WX93-9
	PALLD	NM_016081.4		c.3246T>C	p.Tyr1082Tyr	synonymous	Exon 19 of 21	NP_057165.3
	PALLD	NM_001166109.2		c.2100T>C	p.Tyr700Tyr	synonymous	Exon 18 of 19	NP_001159581.1	Q8WX93-8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PALLD	ENST00000505667.6	TSL:1 MANE Select	c.3297T>C	p.Tyr1099Tyr	synonymous	Exon 20 of 22	ENSP00000425556.1	Q8WX93-9
	PALLD	ENST00000261509.10	TSL:1	c.3246T>C	p.Tyr1082Tyr	synonymous	Exon 19 of 21	ENSP00000261509.6	Q8WX93-2
	PALLD	ENST00000507735.6	TSL:1	c.1785T>C	p.Tyr595Tyr	synonymous	Exon 11 of 12	ENSP00000424016.1	Q8WX93-4

Frequencies

GnomAD3 genomes AF: 0.00534 AC: 812 AN: 152202 Hom.: 12 Cov.: 32

Gnomad AFR AF: 0.000289

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000523

Gnomad ASJ AF: 0.0138

Gnomad EAS AF: 0.00173

Gnomad SAS AF: 0.000828

Gnomad FIN AF: 0.0575

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00165

Gnomad OTH AF: 0.00430

GnomAD2 exomes AF: 0.00634 AC: 1593 AN: 251136 AF XY: 0.00626

Gnomad AFR exome AF: 0.000369

Gnomad AMR exome AF: 0.000231

Gnomad ASJ exome AF: 0.0130

Gnomad EAS exome AF: 0.00114

Gnomad FIN exome AF: 0.0552

Gnomad NFE exome AF: 0.00150

Gnomad OTH exome AF: 0.00930

GnomAD4 exome AF: 0.00279 AC: 4075 AN: 1461782 Hom.: 85 Cov.: 32 AF XY: 0.00272 AC XY: 1980 AN XY: 727204

African (AFR) AF: 0.000119 AC: 4 AN: 33474

American (AMR) AF: 0.000157 AC: 7 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.0132 AC: 345 AN: 26134

East Asian (EAS) AF: 0.00242 AC: 96 AN: 39682

South Asian (SAS) AF: 0.000104 AC: 9 AN: 86258

European-Finnish (FIN) AF: 0.0547 AC: 2920 AN: 53414

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.000406 AC: 451 AN: 1111938

Other (OTH) AF: 0.00402 AC: 243 AN: 60394

GnomAD4 genome AF: 0.00532 AC: 811 AN: 152320 Hom.: 12 Cov.: 32 AF XY: 0.00768 AC XY: 572 AN XY: 74484

African (AFR) AF: 0.000289 AC: 12 AN: 41578

American (AMR) AF: 0.000523 AC: 8 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.0138 AC: 48 AN: 3472

East Asian (EAS) AF: 0.00173 AC: 9 AN: 5190

South Asian (SAS) AF: 0.000829 AC: 4 AN: 4826

European-Finnish (FIN) AF: 0.0575 AC: 610 AN: 10602

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00165 AC: 112 AN: 68022

Other (OTH) AF: 0.00378 AC: 8 AN: 2116

Alfa AF: 0.00288 Hom.: 0

Bravo AF: 0.000839

Asia WGS AF: 0.00231 AC: 8 AN: 3478

EpiCase AF: 0.000545

EpiControl AF: 0.000178

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not specified (2)
-	-	1	not provided (1)
-	-	1	PALLD-related disorder (1)
-	-	1	Pancreatic adenocarcinoma (1)
-	-	1	Pancreatic cancer, susceptibility to, 1 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	0.91
DANN	Benign	0.56
PhyloP100		-0.39
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: rs114593924; hg19: chr4-169846168;