Genetic Variant PALM:c.58-9T>G (chr19-726999-T-G) – 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>G 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 0.0 ( 0 hom., cov: 25)

Exomes 𝑓: 0.000013 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

PALM
NM_002579.3 intron

Scores

Splicing: ADA: 0.001217

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:

Genome browser will be placed here

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=-0.97).

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>G		intron	N/A	NP_002570.2	O75781-1
	PALM	NM_001040134.2		c.58-9T>G		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>G	intron	N/A	ENSP00000341911.4	O75781-1
PALM	ENST00000264560.11	TSL:4	c.58-9T>G	intron	N/A	ENSP00000264560.7	O75781-2
PALM	ENST00000964891.1		c.58-9T>G	intron	N/A	ENSP00000634950.1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

82932

Hom.:

Cov.:

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000131

AC:

AN:

381298

Hom.:

Cov.:

AF XY:

0.0000149

AC XY:

AN XY:

201656

show subpopulations

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

African (AFR)

AF:

0.00

AC:

AN:

9948

American (AMR)

AF:

0.00

AC:

AN:

16866

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

10172

East Asian (EAS)

AF:

0.00

AC:

AN:

11062

South Asian (SAS)

AF:

0.00

AC:

AN:

42236

European-Finnish (FIN)

AF:

0.00

AC:

AN:

26286

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2014

European-Non Finnish (NFE)

AF:

0.0000203

AC:

AN:

246600

Other (OTH)

AF:

0.00

AC:

AN:

16114

⚠️ 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: 0.245

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

82932

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

39920

African (AFR)

AF:

0.00

AC:

AN:

21540

American (AMR)

AF:

0.00

AC:

AN:

6994

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2174

East Asian (EAS)

AF:

0.00

AC:

AN:

3000

South Asian (SAS)

AF:

0.00

AC:

AN:

2524

European-Finnish (FIN)

AF:

0.00

AC:

AN:

3668

Middle Eastern (MID)

AF:

0.00

AC:

AN:

132

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

41290

Other (OTH)

AF:

0.00

AC:

AN:

1060

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.97

CADD

Benign

7.3

(source)

DANN

Benign

0.54

PhyloP100

0.27

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0012

dbscSNV1_RF

Benign

0.094

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over