4-168511315-CTT-C

Variant names:

• chr4-168511315-CTT-C
• rs59029193
• NM_001166108.2:c.-82-107_-82-106delTT

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001166108.2(PALLD):​c.-82-107_-82-106delTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.299 in 587,168 control chromosomes in the GnomAD database, including 27,086 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.29 (6652 hom., cov: 0)
  • Exomes 𝑓: 0.30 (20434 hom.)
• Consequence: PALLD NM_001166108.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.334
• 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 -10 ACMG points.

• BP6: Variant 4-168511315-CTT-C is Benign according to our data. Variant chr4-168511315-CTT-C is described in ClinVar as Benign. ClinVar VariationId is 1289336.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.326 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.-82-107_-82-106delTT		intron	N/A	NP_001159580.1	Q8WX93-9
	PALLD	NM_016081.4		c.-82-107_-82-106delTT		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.-82-107_-82-106delTT		intron	N/A	ENSP00000425556.1	Q8WX93-9
	PALLD	ENST00000261509.10	TSL:1	c.-82-107_-82-106delTT		intron	N/A	ENSP00000261509.6	Q8WX93-2
	PALLD	ENST00000968439.1		c.-75-114_-75-113delTT		intron	N/A	ENSP00000638498.1

Frequencies

GnomAD3 genomes AF: 0.294 AC: 44664 AN: 151862 Hom.: 6645 Cov.: 0

Gnomad AFR AF: 0.249

Gnomad AMI AF: 0.433

Gnomad AMR AF: 0.242

Gnomad ASJ AF: 0.281

Gnomad EAS AF: 0.191

Gnomad SAS AF: 0.223

Gnomad FIN AF: 0.395

Gnomad MID AF: 0.272

Gnomad NFE AF: 0.330

Gnomad OTH AF: 0.280

GnomAD4 exome AF: 0.301 AC: 131070 AN: 435188 Hom.: 20434 AF XY: 0.297 AC XY: 68263 AN XY: 230090

African (AFR) AF: 0.249 AC: 3026 AN: 12148

American (AMR) AF: 0.211 AC: 3754 AN: 17788

Ashkenazi Jewish (ASJ) AF: 0.296 AC: 3966 AN: 13388

East Asian (EAS) AF: 0.196 AC: 5890 AN: 30014

South Asian (SAS) AF: 0.228 AC: 10094 AN: 44226

European-Finnish (FIN) AF: 0.392 AC: 10752 AN: 27396

Middle Eastern (MID) AF: 0.233 AC: 444 AN: 1906

European-Non Finnish (NFE) AF: 0.326 AC: 85677 AN: 263042

Other (OTH) AF: 0.295 AC: 7467 AN: 25280

GnomAD4 genome AF: 0.294 AC: 44693 AN: 151980 Hom.: 6652 Cov.: 0 AF XY: 0.293 AC XY: 21765 AN XY: 74262

African (AFR) AF: 0.250 AC: 10347 AN: 41446

American (AMR) AF: 0.241 AC: 3693 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.281 AC: 973 AN: 3468

East Asian (EAS) AF: 0.190 AC: 986 AN: 5178

South Asian (SAS) AF: 0.223 AC: 1074 AN: 4824

European-Finnish (FIN) AF: 0.395 AC: 4158 AN: 10538

Middle Eastern (MID) AF: 0.286 AC: 84 AN: 294

European-Non Finnish (NFE) AF: 0.330 AC: 22401 AN: 67912

Other (OTH) AF: 0.276 AC: 583 AN: 2110

Alfa AF: 0.317 Hom.: 968

Bravo AF: 0.280

Asia WGS AF: 0.199 AC: 692 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
PhyloP100		0.33
Mutation Taster		=90/10	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: rs59029193; hg19: chr4-169432466; COSMIC: COSV54990853; COSMIC: COSV54990853;