rs12510359

chr4-168756241-A-Gchr4-168756241-A-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001166108.2(PALLD):c.1964+44318A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.496 in 187,304 control chromosomes in the GnomAD database, including 25,933 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.50 (21663 hom., cov: 32)
  • Exomes 𝑓: 0.47 (4270 hom.)
• Consequence: PALLD NM_001166108.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.41

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]

RPL9P16 (HGNC:36851): (ribosomal protein L9 pseudogene 16)

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.68).
• BP6: Variant 4-168756241-A-G is Benign according to our data. Variant chr4-168756241-A-G is described in ClinVar as [Benign]. Clinvar id is 1164338.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.643 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PALLD	NM_001166108.2	c.1964+44318A>G		intron_variant		ENST00000505667.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PALLD	ENST00000505667.6	c.1964+44318A>G		intron_variant		1	NM_001166108.2	A2
RPL9P16	ENST00000491923.1	n.426A>G		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes AF: 0.502 AC: 76235 AN: 151998 Hom.: 21664 Cov.: 32

Gnomad AFR AF: 0.256

Gnomad AMI AF: 0.409

Gnomad AMR AF: 0.509

Gnomad ASJ AF: 0.514

Gnomad EAS AF: 0.165

Gnomad SAS AF: 0.466

Gnomad FIN AF: 0.697

Gnomad MID AF: 0.459

Gnomad NFE AF: 0.648

Gnomad OTH AF: 0.509

GnomAD4 exome AF: 0.472 AC: 16621 AN: 35188 Hom.: 4270 Cov.: 0 AF XY: 0.449 AC XY: 8827 AN XY: 19650

Gnomad4 AFR exome AF: 0.128

Gnomad4 AMR exome AF: 0.333

Gnomad4 ASJ exome AF: 0.353

Gnomad4 EAS exome AF: 0.0955

Gnomad4 SAS exome AF: 0.325

Gnomad4 FIN exome AF: 0.648

Gnomad4 NFE exome AF: 0.527

Gnomad4 OTH exome AF: 0.472

GnomAD4 genome AF: 0.501 AC: 76249 AN: 152116 Hom.: 21663 Cov.: 32 AF XY: 0.500 AC XY: 37147 AN XY: 74360

Gnomad4 AFR AF: 0.256

Gnomad4 AMR AF: 0.509

Gnomad4 ASJ AF: 0.514

Gnomad4 EAS AF: 0.164

Gnomad4 SAS AF: 0.465

Gnomad4 FIN AF: 0.697

Gnomad4 NFE AF: 0.648

Gnomad4 OTH AF: 0.504

Alfa AF: 0.591 Hom.: 10727

Bravo AF: 0.476

Asia WGS AF: 0.312 AC: 1088 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Pancreatic adenocarcinoma Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 29, 2024

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
Cadd	Benign	6.1
Dann	Benign	0.82

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

Publications

LitVar

Other links and lift over

dbSNP: rs12510359; hg19: chr4-169677392; COSMIC: COSV54981504;