Variant chr19-14054207-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001145028.2(PALM3):c.1465A>G(p.Lys489Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000429 in 1,400,016 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: not found (cov: 32)

Exomes 𝑓: 0.0000043 ( 0 hom. )

Consequence

PALM3
NM_001145028.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -4.45

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:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.032714695).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PALM3	NM_001145028.2 linkuse as main transcript	c.1465A>G	p.Lys489Glu	missense_variant	7/7	ENST00000669674.2	NP_001138500.2	A6NDB9
PALM3	NM_001367327.1 linkuse as main transcript	c.1267A>G	p.Lys423Glu	missense_variant	5/5		NP_001354256.1
PALM3	XM_047438763.1 linkuse as main transcript	c.1384A>G	p.Lys462Glu	missense_variant	6/6		XP_047294719.1
PALM3	XM_047438764.1 linkuse as main transcript	c.1267A>G	p.Lys423Glu	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.1465A>G	p.Lys489Glu	missense_variant	7/7		NM_001145028.2	ENSP00000499271.1	A0A590UJ36
PALM3	ENST00000340790.9 linkuse as main transcript	c.1420A>G	p.Lys474Glu	missense_variant	6/6	5		ENSP00000344996.3	A6NDB9
PALM3	ENST00000661591.1 linkuse as main transcript	c.1345A>G	p.Lys449Glu	missense_variant	4/4			ENSP00000499248.1	A0A590UJ23
PALM3	ENST00000589048.2 linkuse as main transcript	c.1267A>G	p.Lys423Glu	missense_variant	5/5	3		ENSP00000465701.2	K7EKN5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000126

AC:

AN:

159078

Hom.:

AF XY:

0.0000239

AC XY:

AN XY:

83732

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000322

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000429

AC:

AN:

1400016

Hom.:

Cov.:

AF XY:

0.00000434

AC XY:

AN XY:

690496

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:

0.00000463

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000492

Hom.:

Bravo

AF:

0.00000378

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

Jul 27, 2024

The c.1420A>G (p.K474E) alteration is located in exon 6 (coding exon 6) of the PALM3 gene. This alteration results from a A to G substitution at nucleotide position 1420, causing the lysine (K) at amino acid position 474 to be replaced by a glutamic acid (E). 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

0.072

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.70

CADD

Benign

0.024

DANN

Benign

0.64

DEOGEN2

Benign

0.0027

Eigen

Benign

-2.0

Eigen_PC

Benign

-2.0

FATHMM_MKL

Benign

0.011

LIST_S2

Benign

0.26

M_CAP

Benign

0.0063

MetaRNN

Benign

0.033

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.55

PrimateAI

Benign

0.23

PROVEAN

Benign

0.050

REVEL

Benign

0.025

Sift

Benign

0.30

Sift4G

Benign

1.0

Polyphen

0.0010

Vest4

0.091

MutPred

0.17

Loss of ubiquitination at K474 (P = 0.0059);

MVP

0.067

ClinPred

0.48

GERP RS

-8.8

Varity_R

0.046

gMVP

0.024

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