Variant 19-14053943-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001145028.2(PALM3):c.1729C>A(p.Leu577Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000387 in 1,551,500 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000029 ( 0 hom. )

Consequence

PALM3
NM_001145028.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.195

Variant links:

Genes affected

PALM3 (HGNC:33274): (paralemmin 3) Predicted to enable ATP binding activity. Involved in Toll signaling pathway; negative regulation of cytokine-mediated signaling pathway; and response to lipopolysaccharide. Predicted to be located in cytoplasm and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

PALM3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.087970525).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PALM3	NM_001145028.2 linkuse as main transcript	c.1729C>A	p.Leu577Ile	missense_variant	7/7	ENST00000669674.2	NP_001138500.2	A6NDB9
PALM3	NM_001367327.1 linkuse as main transcript	c.1531C>A	p.Leu511Ile	missense_variant	5/5		NP_001354256.1
PALM3	XM_047438763.1 linkuse as main transcript	c.1648C>A	p.Leu550Ile	missense_variant	6/6		XP_047294719.1
PALM3	XM_047438764.1 linkuse as main transcript	c.1531C>A	p.Leu511Ile	missense_variant	5/5		XP_047294720.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
PALM3	ENST00000669674.2 linkuse as main transcript	c.1729C>A	p.Leu577Ile	missense_variant	7/7		NM_001145028.2	ENSP00000499271.1	A0A590UJ36
PALM3	ENST00000340790.9 linkuse as main transcript	c.1684C>A	p.Leu562Ile	missense_variant	6/6	5		ENSP00000344996.3	A6NDB9
PALM3	ENST00000661591.1 linkuse as main transcript	c.1609C>A	p.Leu537Ile	missense_variant	4/4			ENSP00000499248.1	A0A590UJ23
PALM3	ENST00000589048.2 linkuse as main transcript	c.1531C>A	p.Leu511Ile	missense_variant	5/5	3		ENSP00000465701.2	K7EKN5

Frequencies

GnomAD3 genomes

AF:

0.0000132

AC:

AN:

152082

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000286

AC:

AN:

1399418

Hom.:

Cov.:

AF XY:

0.00000435

AC XY:

AN XY:

690218

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000371

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000132

AC:

AN:

152082

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74294

show subpopulations

Gnomad4 AFR

AF:

0.0000242

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 03, 2024

The c.1684C>A (p.L562I) alteration is located in exon 6 (coding exon 6) of the PALM3 gene. This alteration results from a C to A substitution at nucleotide position 1684, causing the leucine (L) at amino acid position 562 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.096

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.67

CADD

Benign

0.81

DANN

Benign

0.92

DEOGEN2

Benign

0.0052

Eigen

Benign

-0.77

Eigen_PC

Benign

-0.88

FATHMM_MKL

Benign

0.15

LIST_S2

Benign

0.41

M_CAP

Benign

0.0075

MetaRNN

Benign

0.088

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.6

PrimateAI

Benign

0.29

PROVEAN

Benign

-0.46

REVEL

Benign

0.038

Sift

Benign

0.070

Sift4G

Benign

0.49

Polyphen

0.57

Vest4

0.10

MutPred

0.19

Gain of sheet (P = 0.0477);

MVP

0.014

ClinPred

0.12

GERP RS

-0.61

Varity_R

0.059

gMVP

0.022

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over