Variant 19-14053853-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.1819C>T(p.Pro607Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000967 in 1,551,158 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 0.000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000036 ( 0 hom. )

Consequence

PALM3
NM_001145028.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.62

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 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=0.054686457).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
PALM3	NM_001145028.2 linkuse as main transcript	c.1819C>T	p.Pro607Ser	missense_variant	7/7	ENST00000669674.2
PALM3	NM_001367327.1 linkuse as main transcript	c.1621C>T	p.Pro541Ser	missense_variant	5/5
PALM3	XM_047438763.1 linkuse as main transcript	c.1738C>T	p.Pro580Ser	missense_variant	6/6
PALM3	XM_047438764.1 linkuse as main transcript	c.1621C>T	p.Pro541Ser	missense_variant	5/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
PALM3	ENST00000669674.2 linkuse as main transcript	c.1819C>T	p.Pro607Ser	missense_variant	7/7		NM_001145028.2	A2
PALM3	ENST00000340790.9 linkuse as main transcript	c.1774C>T	p.Pro592Ser	missense_variant	6/6	5		P4
PALM3	ENST00000661591.1 linkuse as main transcript	c.1699C>T	p.Pro567Ser	missense_variant	4/4			A2
PALM3	ENST00000589048.2 linkuse as main transcript	c.1621C>T	p.Pro541Ser	missense_variant	5/5	3		A2

Frequencies

GnomAD3 genomes

AF:

0.0000658

AC:

AN:

152004

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000242

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000130

AC:

AN:

153974

Hom.:

AF XY:

0.00

AC XY:

AN XY:

81642

show subpopulations

Gnomad AFR exome

AF:

0.000126

Gnomad AMR exome

AF:

0.0000405

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000357

AC:

AN:

1399154

Hom.:

Cov.:

AF XY:

0.00000145

AC XY:

AN XY:

690096

show subpopulations

Gnomad4 AFR exome

AF:

0.0000950

Gnomad4 AMR exome

AF:

0.0000280

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:

0.0000172

GnomAD4 genome

AF:

0.0000658

AC:

AN:

152004

Hom.:

Cov.:

AF XY:

0.0000808

AC XY:

AN XY:

74236

show subpopulations

Gnomad4 AFR

AF:

0.000242

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:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000132

Hom.:

Bravo

AF:

0.0000869

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

Apr 25, 2023

The c.1774C>T (p.P592S) 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 1774, causing the proline (P) at amino acid position 592 to be replaced by a serine (S). 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

-0.47

BayesDel_noAF

Benign

-0.68

Cadd

Benign

Dann

Benign

0.65

DEOGEN2

Benign

0.0042

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.10

LIST_S2

Benign

0.47

M_CAP

Benign

0.0088

MetaRNN

Benign

0.055

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.81

MutationTaster

Benign

1.0

PrimateAI

Benign

0.39

PROVEAN

Uncertain

-3.1

REVEL

Benign

0.022

Sift

Benign

0.054

Sift4G

Benign

0.14

Polyphen

0.0050

Vest4

0.059

MVP

0.030

ClinPred

0.019

GERP RS

-0.23

Varity_R

0.054

gMVP

0.13

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