Genetic Variant NM_002579.3:c.58-9T>A (chr19-726999-T-A) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_002579.3(PALM):c.58-9T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.00028 ( 0 hom., cov: 25)

Exomes 𝑓: 0.0063 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

PALM
NM_002579.3 intron

Scores

Splicing: ADA: 0.004078

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.267

Publications

0 publications found

Variant links:

Genes affected

PALM (HGNC:8594): (paralemmin) This gene encodes a member of the paralemmin protein family. The product of this gene is a prenylated and palmitoylated phosphoprotein that associates with the cytoplasmic face of plasma membranes and is implicated in plasma membrane dynamics in neurons and other cell types. Several alternatively spliced transcript variants have been identified, but the full-length nature of only two transcript variants has been determined. [provided by RefSeq, Jul 2008]

PALM links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.96).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002579.3. 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
	PALM	NM_002579.3	MANE Select	c.58-9T>A		intron	N/A	NP_002570.2	O75781-1
	PALM	NM_001040134.2		c.58-9T>A		intron	N/A	NP_001035224.1	O75781-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
PALM	ENST00000338448.10	TSL:1 MANE Select	c.58-9T>A	intron	N/A	ENSP00000341911.4	O75781-1
PALM	ENST00000264560.11	TSL:4	c.58-9T>A	intron	N/A	ENSP00000264560.7	O75781-2
PALM	ENST00000964891.1		c.58-9T>A	intron	N/A	ENSP00000634950.1

Frequencies

GnomAD3 genomes

AF:

0.000277

AC:

AN:

82900

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000464

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000286

Gnomad ASJ

AF:

0.000460

Gnomad EAS

AF:

0.000333

Gnomad SAS

AF:

0.000397

Gnomad FIN

AF:

0.000545

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000315

Gnomad OTH

AF:

0.00189

GnomAD4 exome

AF:

0.00626

AC:

2341

AN:

374022

Hom.:

Cov.:

AF XY:

0.00586

AC XY:

1162

AN XY:

198130

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00530

AC:

AN:

9810

American (AMR)

AF:

0.00155

AC:

AN:

16788

Ashkenazi Jewish (ASJ)

AF:

0.00427

AC:

AN:

10064

East Asian (EAS)

AF:

0.00828

AC:

AN:

10864

South Asian (SAS)

AF:

0.000902

AC:

AN:

42124

European-Finnish (FIN)

AF:

0.000878

AC:

AN:

26200

Middle Eastern (MID)

AF:

0.00402

AC:

AN:

1990

European-Non Finnish (NFE)

AF:

0.00815

AC:

1960

AN:

240364

Other (OTH)

AF:

0.00639

AC:

101

AN:

15818

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.261

Heterozygous variant carriers

268

537

805

1074

1342

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

164

246

328

410

<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

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000277

AC:

AN:

82962

Hom.:

Cov.:

AF XY:

0.000325

AC XY:

AN XY:

39940

show subpopulations

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.0000464

AC:

AN:

21570

American (AMR)

AF:

0.000286

AC:

AN:

7004

Ashkenazi Jewish (ASJ)

AF:

0.000460

AC:

AN:

2174

East Asian (EAS)

AF:

0.000332

AC:

AN:

3008

South Asian (SAS)

AF:

0.000396

AC:

AN:

2524

European-Finnish (FIN)

AF:

0.000545

AC:

AN:

3668

Middle Eastern (MID)

AF:

0.00

AC:

AN:

124

European-Non Finnish (NFE)

AF:

0.000315

AC:

AN:

41272

Other (OTH)

AF:

0.00187

AC:

AN:

1068

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.279

Heterozygous variant carriers

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

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.96

CADD

Benign

7.0

(source)

DANN

Benign

0.67

PhyloP100

0.27

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0041

dbscSNV1_RF

Benign

0.13

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

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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