Genetic Variant PALM:c.58-13G>A (chr19-726995-G-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_002579.3(PALM):c.58-13G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000531 in 753,664 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.0000069 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0000049 ( 0 hom. )

Consequence

PALM
NM_002579.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.180

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 -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PALM	NM_002579.3 link	c.58-13G>A		intron_variant	Intron 2 of 8	ENST00000338448.10	NP_002570.2	O75781-1A0A024R1Y6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PALM	ENST00000338448.10 link	c.58-13G>A		intron_variant	Intron 2 of 8	1	NM_002579.3	ENSP00000341911.4		O75781-1

Frequencies

GnomAD3 genomes

AF:

0.00000688

AC:

AN:

145312

Hom.:

Cov.:

show subpopulations

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:

0.0000151

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000493

AC:

AN:

608352

Hom.:

Cov.:

AF XY:

0.00000945

AC XY:

AN XY:

317598

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:

14644

American (AMR)

AF:

0.00

AC:

AN:

28854

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

13848

East Asian (EAS)

AF:

0.00

AC:

AN:

14680

South Asian (SAS)

AF:

0.00

AC:

AN:

65270

European-Finnish (FIN)

AF:

0.00

AC:

AN:

30098

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2524

European-Non Finnish (NFE)

AF:

0.00000726

AC:

AN:

413404

Other (OTH)

AF:

0.00

AC:

AN:

25030

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.225

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00000688

AC:

AN:

145312

Hom.:

Cov.:

AF XY:

0.0000141

AC XY:

AN XY:

70806

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

40242

American (AMR)

AF:

0.00

AC:

AN:

14686

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3388

East Asian (EAS)

AF:

0.00

AC:

AN:

4338

South Asian (SAS)

AF:

0.00

AC:

AN:

4060

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9282

Middle Eastern (MID)

AF:

0.00

AC:

AN:

304

European-Non Finnish (NFE)

AF:

0.0000151

AC:

AN:

66106

Other (OTH)

AF:

0.00

AC:

AN:

2032

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.675

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

1.4

(source)

DANN

Benign

0.38

PhyloP100

-0.18

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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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chr19-726995-G-A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over