Variant 19-14054434-G-A 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.1238C>T(p.Ala413Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000122 in 1,551,312 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 0.000046 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000086 ( 0 hom. )

Consequence

PALM3
NM_001145028.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.41

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=0.023995906).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
PALM3	NM_001145028.2 linkuse as main transcript	c.1238C>T	p.Ala413Val	missense_variant	7/7	ENST00000669674.2
PALM3	NM_001367327.1 linkuse as main transcript	c.1040C>T	p.Ala347Val	missense_variant	5/5
PALM3	XM_047438763.1 linkuse as main transcript	c.1157C>T	p.Ala386Val	missense_variant	6/6
PALM3	XM_047438764.1 linkuse as main transcript	c.1040C>T	p.Ala347Val	missense_variant	5/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
PALM3	ENST00000669674.2 linkuse as main transcript	c.1238C>T	p.Ala413Val	missense_variant	7/7		NM_001145028.2	A2
PALM3	ENST00000340790.9 linkuse as main transcript	c.1193C>T	p.Ala398Val	missense_variant	6/6	5		P4
PALM3	ENST00000661591.1 linkuse as main transcript	c.1118C>T	p.Ala373Val	missense_variant	4/4			A2
PALM3	ENST00000589048.2 linkuse as main transcript	c.1040C>T	p.Ala347Val	missense_variant	5/5	3		A2

Frequencies

GnomAD3 genomes

AF:

0.0000462

AC:

AN:

151628

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000485

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00104

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000127

AC:

AN:

158000

Hom.:

AF XY:

0.0000120

AC XY:

AN XY:

83396

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000404

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:

0.0000163

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000857

AC:

AN:

1399684

Hom.:

Cov.:

AF XY:

0.0000101

AC XY:

AN XY:

690354

show subpopulations

Gnomad4 AFR exome

AF:

0.0000316

Gnomad4 AMR exome

AF:

0.0000280

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000757

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000371

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000462

AC:

AN:

151628

Hom.:

Cov.:

AF XY:

0.0000676

AC XY:

AN XY:

74018

show subpopulations

Gnomad4 AFR

AF:

0.0000485

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00104

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000189

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

May 31, 2023

The c.1193C>T (p.A398V) 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 1193, causing the alanine (A) at amino acid position 398 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

0.10

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.76

Cadd

Benign

3.2

Dann

Benign

0.90

DEOGEN2

Benign

0.0022

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.032

LIST_S2

Benign

0.41

M_CAP

Benign

0.0046

MetaRNN

Benign

0.024

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.47

MutationTaster

Benign

1.0

PrimateAI

Benign

0.24

PROVEAN

Benign

-0.75

REVEL

Benign

0.020

Sift

Benign

0.66

Sift4G

Benign

0.32

Polyphen

0.078

Vest4

0.039

MutPred

0.25

Gain of methylation at K397 (P = 0.0392);

MVP

0.014

ClinPred

0.036

GERP RS

-9.8

Varity_R

0.033

gMVP

0.016

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