Variant 19-14054161-T-C 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.1511A>G(p.Glu504Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000029 in 1,551,642 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 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: 0.000031 ( 0 hom. )

Consequence

PALM3
NM_001145028.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.241

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=0.09691021).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PALM3	NM_001145028.2 linkuse as main transcript	c.1511A>G	p.Glu504Gly	missense_variant	7/7	ENST00000669674.2	NP_001138500.2	A6NDB9
PALM3	NM_001367327.1 linkuse as main transcript	c.1313A>G	p.Glu438Gly	missense_variant	5/5		NP_001354256.1
PALM3	XM_047438763.1 linkuse as main transcript	c.1430A>G	p.Glu477Gly	missense_variant	6/6		XP_047294719.1
PALM3	XM_047438764.1 linkuse as main transcript	c.1313A>G	p.Glu438Gly	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.1511A>G	p.Glu504Gly	missense_variant	7/7		NM_001145028.2	ENSP00000499271.1	A0A590UJ36
PALM3	ENST00000340790.9 linkuse as main transcript	c.1466A>G	p.Glu489Gly	missense_variant	6/6	5		ENSP00000344996.3	A6NDB9
PALM3	ENST00000661591.1 linkuse as main transcript	c.1391A>G	p.Glu464Gly	missense_variant	4/4			ENSP00000499248.1	A0A590UJ23
PALM3	ENST00000589048.2 linkuse as main transcript	c.1313A>G	p.Glu438Gly	missense_variant	5/5	3		ENSP00000465701.2	K7EKN5

Frequencies

GnomAD3 genomes

AF:

0.00000659

AC:

AN:

151804

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

GnomAD3 exomes

AF:

0.0000127

AC:

AN:

158016

Hom.:

AF XY:

0.0000120

AC XY:

AN XY:

83246

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:

0.0000325

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000314

AC:

AN:

1399838

Hom.:

Cov.:

AF XY:

0.0000275

AC XY:

AN XY:

690416

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:

0.0000408

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000659

AC:

AN:

151804

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74112

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

Alfa

AF:

0.0000564

Hom.:

Bravo

AF:

0.0000264

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 24, 2023

The c.1466A>G (p.E489G) 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 1466, causing the glutamic acid (E) at amino acid position 489 to be replaced by a glycine (G). 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

0.093

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.57

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.0026

Eigen

Benign

-0.88

Eigen_PC

Benign

-0.92

FATHMM_MKL

Benign

0.15

LIST_S2

Benign

0.51

M_CAP

Benign

0.012

MetaRNN

Benign

0.097

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.5

PrimateAI

Benign

0.28

PROVEAN

Benign

-2.0

REVEL

Benign

0.015

Sift

Benign

0.14

Sift4G

Benign

0.087

Polyphen

0.093

Vest4

0.11

MutPred

0.28

Loss of sheet (P = 0.0104);

MVP

0.32

ClinPred

0.052

GERP RS

0.95

Varity_R

0.085

gMVP

0.033

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