rs62333818

Variant names:

• chr4-168497281-T-C
• rs62333818
• NM_001166108.2:c.-83+87T>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001166108.2(PALLD):​c.-83+87T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0967 in 152,070 control chromosomes in the GnomAD database, including 804 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.097 (804 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: PALLD NM_001166108.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.00700
• 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]

DDX60L (HGNC:26429): (DExD/H-box 60 like) This gene encodes a member of the DExD/H-box helicase family of proteins, a subset of the super family 2 helicases. Members of the DExD/H-box helicase family share a conserved functional core comprised of two RecA-like globular domains. These domains contain conserved motifs that mediate ATP binding, ATP hydrolysis, nucleic acid binding, and RNA unwinding. In addition to functions in RNA metabolism, members of this family are involved in anti-viral immunity and act as cytosolic sensors of viral nucleic acids. The protein encoded by this gene has been shown to inhibit hepatitis C virus replication in response to interferon stimulation in cell culture. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2016]

LOC107986198 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 4-168497281-T-C is Benign according to our data. Variant chr4-168497281-T-C is described in ClinVar as Benign. ClinVar VariationId is 1226420.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.107 is higher than 0.05.

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.-83+87T>C		intron	N/A	NP_001159580.1	Q8WX93-9
	PALLD	NM_016081.4		c.-83+87T>C		intron	N/A	NP_057165.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PALLD	ENST00000505667.6	TSL:1 MANE Select	c.-83+87T>C		intron	N/A	ENSP00000425556.1	Q8WX93-9
	PALLD	ENST00000261509.10	TSL:1	c.-83+87T>C		intron	N/A	ENSP00000261509.6	Q8WX93-2
	PALLD	ENST00000968439.1		c.-76+87T>C		intron	N/A	ENSP00000638498.1

Frequencies

GnomAD3 genomes AF: 0.0968 AC: 14703 AN: 151952 Hom.: 804 Cov.: 32

Gnomad AFR AF: 0.0897

Gnomad AMI AF: 0.156

Gnomad AMR AF: 0.0535

Gnomad ASJ AF: 0.0432

Gnomad EAS AF: 0.0333

Gnomad SAS AF: 0.0525

Gnomad FIN AF: 0.176

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.109

Gnomad OTH AF: 0.0837

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0967 AC: 14705 AN: 152070 Hom.: 804 Cov.: 32 AF XY: 0.0967 AC XY: 7184 AN XY: 74322

African (AFR) AF: 0.0896 AC: 3721 AN: 41522

American (AMR) AF: 0.0533 AC: 814 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0432 AC: 150 AN: 3472

East Asian (EAS) AF: 0.0336 AC: 174 AN: 5176

South Asian (SAS) AF: 0.0526 AC: 254 AN: 4830

European-Finnish (FIN) AF: 0.176 AC: 1844 AN: 10492

Middle Eastern (MID) AF: 0.0374 AC: 11 AN: 294

European-Non Finnish (NFE) AF: 0.109 AC: 7420 AN: 67972

Other (OTH) AF: 0.0828 AC: 175 AN: 2114

Alfa AF: 0.0995 Hom.: 289

Bravo AF: 0.0881

Asia WGS AF: 0.0480 AC: 166 AN: 3476

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	5.4
DANN	Benign	0.63
PhyloP100		0.0070
PromoterAI		-0.0037	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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: rs62333818; hg19: chr4-169418432;