Variant chr19-14054308-G-A 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.1364C>T(p.Ala455Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000659 in 151,694 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. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

PALM3
NM_001145028.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.609

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 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=0.07367697).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PALM3	NM_001145028.2 linkuse as main transcript	c.1364C>T	p.Ala455Val	missense_variant	7/7	ENST00000669674.2	NP_001138500.2	A6NDB9
PALM3	NM_001367327.1 linkuse as main transcript	c.1166C>T	p.Ala389Val	missense_variant	5/5		NP_001354256.1
PALM3	XM_047438763.1 linkuse as main transcript	c.1283C>T	p.Ala428Val	missense_variant	6/6		XP_047294719.1
PALM3	XM_047438764.1 linkuse as main transcript	c.1166C>T	p.Ala389Val	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.1364C>T	p.Ala455Val	missense_variant	7/7		NM_001145028.2	ENSP00000499271.1	A0A590UJ36
PALM3	ENST00000340790.9 linkuse as main transcript	c.1319C>T	p.Ala440Val	missense_variant	6/6	5		ENSP00000344996.3	A6NDB9
PALM3	ENST00000661591.1 linkuse as main transcript	c.1244C>T	p.Ala415Val	missense_variant	4/4			ENSP00000499248.1	A0A590UJ23
PALM3	ENST00000589048.2 linkuse as main transcript	c.1166C>T	p.Ala389Val	missense_variant	5/5	3		ENSP00000465701.2	K7EKN5

Frequencies

GnomAD3 genomes

AF:

0.00000659

AC:

AN:

151694

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1400076

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

690520

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000659

AC:

AN:

151694

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74060

show subpopulations

Gnomad4 AFR

AF:

0.00

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

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

Dec 28, 2022

The c.1319C>T (p.A440V) alteration is located in exon 6 (coding exon 6) of the PALM3 gene. This alteration results from a C to T substitution at nucleotide position 1319, causing the alanine (A) at amino acid position 440 to be replaced by a valine (V). 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

0.084

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.76

CADD

Benign

4.0

DANN

Benign

0.96

DEOGEN2

Benign

0.0028

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.049

LIST_S2

Benign

0.53

M_CAP

Benign

0.028

MetaRNN

Benign

0.074

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.69

PrimateAI

Benign

0.23

PROVEAN

Benign

-0.56

REVEL

Benign

0.019

Sift

Benign

0.040

Sift4G

Benign

0.45

Polyphen

0.32

Vest4

0.033

MutPred

0.25

Gain of sheet (P = 0.0125);

MVP

0.014

ClinPred

0.13

GERP RS

-2.2

Varity_R

0.035

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