Genetic Variant PALM:p.Thr154Lys (chr19-736037-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_002579.3(PALM):c.461C>A(p.Thr154Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,458,236 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T154M) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 30)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

PALM
NM_002579.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.405

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: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.2356346).

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.461C>A	p.Thr154Lys	missense	Exon 7 of 9	NP_002570.2	O75781-1
	PALM	NM_001040134.2		c.461C>A	p.Thr154Lys	missense	Exon 7 of 8	NP_001035224.1	O75781-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PALM	ENST00000338448.10	TSL:1 MANE Select	c.461C>A	p.Thr154Lys	missense	Exon 7 of 9	ENSP00000341911.4	O75781-1
PALM	ENST00000264560.11	TSL:4	c.461C>A	p.Thr154Lys	missense	Exon 7 of 8	ENSP00000264560.7	O75781-2
PALM	ENST00000964891.1		c.440C>A	p.Thr147Lys	missense	Exon 7 of 8	ENSP00000634950.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.86e-7

AC:

AN:

1458236

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

725368

show subpopulations

African (AFR)

AF:

0.0000300

AC:

AN:

33334

American (AMR)

AF:

0.00

AC:

AN:

44280

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25992

East Asian (EAS)

AF:

0.00

AC:

AN:

39402

South Asian (SAS)

AF:

0.00

AC:

AN:

85662

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53350

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5758

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1110218

Other (OTH)

AF:

0.00

AC:

AN:

60240

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

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

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.68

CADD

Benign

8.2

(source)

DANN

Benign

0.86

DEOGEN2

Benign

0.064

Eigen

Benign

-0.81

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.048

LIST_S2

Benign

0.74

M_CAP

Benign

0.040

MetaRNN

Benign

0.24

MetaSVM

Benign

-0.91

MutationAssessor

Uncertain

2.6

PhyloP100

0.41

PrimateAI

Benign

0.41

PROVEAN

Benign

-2.3

REVEL

Benign

0.067

Sift

Benign

0.11

Sift4G

Uncertain

0.057

Polyphen

0.93

Vest4

0.39

MutPred

0.43

Loss of phosphorylation at T154 (P = 0.0111)

MVP

0.31

MPC

0.52

ClinPred

0.62

GERP RS

-2.5

Varity_R

0.062

gMVP

0.55

Mutation Taster

=85/15

polymorphism

(source)

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

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over