dbSNP rs201979617: PALLD:p.Pro115dup (chr4-168878227-G-GCCA) – ACMG Classification: Benign (-15 pts)

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 1P and 16B. PM4_SupportingBP6_Very_StrongBS1BS2

The NM_001166110.2(PALLD):c.342_344dupACC(p.Pro115dup) variant causes a disruptive inframe insertion change. The variant allele was found at a frequency of 0.00196 in 1,478,304 control chromosomes in the GnomAD database, including 31 homozygotes. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. P115P) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0055 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0016 ( 30 hom. )

Consequence

PALLD
NM_001166110.2 disruptive_inframe_insertion

Scores

Not classified

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 7.07

Publications

0 publications found

Variant links:

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]

PALLD links:

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]

CBR4 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -15 ACMG points.

PM4

Nonframeshift variant in NON repetitive region in NM_001166110.2. Strenght limited to Supporting due to length of the change: 1aa.

BP6

Variant 4-168878227-G-GCCA is Benign according to our data. Variant chr4-168878227-G-GCCA is described in ClinVar as Benign. ClinVar VariationId is 476388.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.00547 (798/145980) while in subpopulation SAS AF = 0.022 (96/4370). AF 95% confidence interval is 0.0184. There are 1 homozygotes in GnomAd4. There are 398 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High AC in GnomAd4 at 798 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001166110.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
PALLD	NM_001166108.2	MANE Select	c.1965-12689_1965-12687dupACC		intron	N/A	NP_001159580.1
PALLD	NM_001166110.2		c.342_344dupACC	p.Pro115dup	disruptive_inframe_insertion	Exon 2 of 12	NP_001159582.1
PALLD	NM_016081.4		c.1965-12689_1965-12687dupACC		intron	N/A	NP_057165.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
PALLD	ENST00000507735.6	TSL:1	c.342_344dupACC	p.Pro115dup	disruptive_inframe_insertion	Exon 2 of 12	ENSP00000424016.1
PALLD	ENST00000505667.6	TSL:1 MANE Select	c.1965-12689_1965-12687dupACC		intron	N/A	ENSP00000425556.1
PALLD	ENST00000261509.10	TSL:1	c.1965-12689_1965-12687dupACC		intron	N/A	ENSP00000261509.6

Frequencies

GnomAD3 genomes

AF:

0.00545

AC:

795

AN:

145908

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0162

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00274

Gnomad ASJ

AF:

0.000289

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0219

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00329

Gnomad NFE

AF:

0.000283

Gnomad OTH

AF:

0.00492

GnomAD2 exomes

AF:

0.00398

AC:

446

AN:

112030

AF XY:

0.00504

show subpopulations

Gnomad AFR exome

AF:

0.0150

Gnomad AMR exome

AF:

0.00144

Gnomad ASJ exome

AF:

0.000537

Gnomad EAS exome

AF:

0.000244

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000715

Gnomad OTH exome

AF:

0.00321

GnomAD4 exome

AF:

0.00158

AC:

2100

AN:

1332324

Hom.:

Cov.:

AF XY:

0.00203

AC XY:

1332

AN XY:

657616

show subpopulations

African (AFR)

AF:

0.0166

AC:

461

AN:

27746

American (AMR)

AF:

0.00152

AC:

AN:

32938

Ashkenazi Jewish (ASJ)

AF:

0.000393

AC:

AN:

22888

East Asian (EAS)

AF:

0.000129

AC:

AN:

31006

South Asian (SAS)

AF:

0.0167

AC:

1276

AN:

76508

European-Finnish (FIN)

AF:

0.00

AC:

AN:

31760

Middle Eastern (MID)

AF:

0.00323

AC:

AN:

4030

European-Non Finnish (NFE)

AF:

0.000121

AC:

127

AN:

1050956

Other (OTH)

AF:

0.00294

AC:

160

AN:

54492

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

121

241

362

482

603

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

102

136

170

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00547

AC:

798

AN:

145980

Hom.:

Cov.:

AF XY:

0.00559

AC XY:

398

AN XY:

71232

show subpopulations

African (AFR)

AF:

0.0163

AC:

631

AN:

38754

American (AMR)

AF:

0.00274

AC:

AN:

14616

Ashkenazi Jewish (ASJ)

AF:

0.000289

AC:

AN:

3458

East Asian (EAS)

AF:

0.00

AC:

AN:

4684

South Asian (SAS)

AF:

0.0220

AC:

AN:

4370

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9810

Middle Eastern (MID)

AF:

0.00352

AC:

AN:

284

European-Non Finnish (NFE)

AF:

0.000283

AC:

AN:

67056

Other (OTH)

AF:

0.00488

AC:

AN:

2050

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

111

148

185

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00246

Hom.:

Asia WGS

AF:

0.00696

AC:

AN:

3462

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (2)

not provided (1)

Pancreatic adenocarcinoma (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

7.1

Mutation Taster

=50/50

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over