chr4-168511143-C-T

Variant names:

• chr4-168511143-C-T
• rs75967573
• NM_001166108.2:c.-82-280C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001166108.2(PALLD):​c.-82-280C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0591 in 152,162 control chromosomes in the GnomAD database, including 339 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.059 (339 hom., cov: 32)
• Consequence: PALLD NM_001166108.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.636
• 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 4-168511143-C-T is Benign according to our data. Variant chr4-168511143-C-T is described in ClinVar as Benign. ClinVar VariationId is 1295087.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.178 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.-82-280C>T		intron	N/A	NP_001159580.1	Q8WX93-9
	PALLD	NM_016081.4		c.-82-280C>T		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.-82-280C>T		intron	N/A	ENSP00000425556.1	Q8WX93-9
	PALLD	ENST00000261509.10	TSL:1	c.-82-280C>T		intron	N/A	ENSP00000261509.6	Q8WX93-2
	PALLD	ENST00000968439.1		c.-75-287C>T		intron	N/A	ENSP00000638498.1

Frequencies

GnomAD3 genomes AF: 0.0592 AC: 9003 AN: 152044 Hom.: 341 Cov.: 32

Gnomad AFR AF: 0.0142

Gnomad AMI AF: 0.0132

Gnomad AMR AF: 0.0745

Gnomad ASJ AF: 0.0643

Gnomad EAS AF: 0.189

Gnomad SAS AF: 0.0477

Gnomad FIN AF: 0.0759

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.0721

Gnomad OTH AF: 0.0541

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

GnomAD4 genome AF: 0.0591 AC: 8996 AN: 152162 Hom.: 339 Cov.: 32 AF XY: 0.0608 AC XY: 4519 AN XY: 74366

African (AFR) AF: 0.0142 AC: 589 AN: 41532

American (AMR) AF: 0.0744 AC: 1136 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.0643 AC: 223 AN: 3466

East Asian (EAS) AF: 0.188 AC: 972 AN: 5168

South Asian (SAS) AF: 0.0479 AC: 231 AN: 4818

European-Finnish (FIN) AF: 0.0759 AC: 802 AN: 10570

Middle Eastern (MID) AF: 0.0612 AC: 18 AN: 294

European-Non Finnish (NFE) AF: 0.0721 AC: 4901 AN: 68012

Other (OTH) AF: 0.0530 AC: 112 AN: 2112

Alfa AF: 0.0601 Hom.: 54

Bravo AF: 0.0567

Asia WGS AF: 0.100 AC: 349 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.58
DANN	Benign	0.37
PhyloP100		-0.64
PromoterAI		-0.0073	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: rs75967573; hg19: chr4-169432294;