Variant 19-14054420-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_001145028.2(PALM3):c.1252G>C(p.Gly418Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000838 in 1,551,850 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 Likely benign (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000086 ( 0 hom. )

Consequence

PALM3
NM_001145028.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.396

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 -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.04626164).

BP6

Variant 19-14054420-C-G is Benign according to our data. Variant chr19-14054420-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 3413749.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PALM3	NM_001145028.2 link	c.1252G>C	p.Gly418Arg	missense_variant	7/7	ENST00000669674.2	NP_001138500.2	A6NDB9
PALM3	NM_001367327.1 link	c.1054G>C	p.Gly352Arg	missense_variant	5/5		NP_001354256.1
PALM3	XM_047438763.1 link	c.1171G>C	p.Gly391Arg	missense_variant	6/6		XP_047294719.1
PALM3	XM_047438764.1 link	c.1054G>C	p.Gly352Arg	missense_variant	5/5		XP_047294720.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
PALM3	ENST00000669674.2 link	c.1252G>C	p.Gly418Arg	missense_variant	7/7		NM_001145028.2	ENSP00000499271.1	A0A590UJ36
PALM3	ENST00000340790.9 link	c.1207G>C	p.Gly403Arg	missense_variant	6/6	5		ENSP00000344996.3	A6NDB9
PALM3	ENST00000661591.1 link	c.1132G>C	p.Gly378Arg	missense_variant	4/4			ENSP00000499248.1	A0A590UJ23
PALM3	ENST00000589048.2 link	c.1054G>C	p.Gly352Arg	missense_variant	5/5	3		ENSP00000465701.2	K7EKN5

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152098

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

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:

0.0000758

AC:

AN:

158346

Hom.:

AF XY:

0.0000718

AC XY:

AN XY:

83524

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000485

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:

0.00000857

AC:

AN:

1399752

Hom.:

Cov.:

AF XY:

0.00000869

AC XY:

AN XY:

690398

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000336

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:

0.00000657

AC:

AN:

152098

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74304

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000655

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

Bravo

AF:

0.0000340

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 10, 2024

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.59

CADD

Benign

9.6

DANN

Benign

0.48

DEOGEN2

Benign

0.0081

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.13

LIST_S2

Benign

0.46

M_CAP

Benign

0.0077

MetaRNN

Benign

0.046

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.3

PrimateAI

Benign

0.25

PROVEAN

Benign

-1.2

REVEL

Benign

0.022

Sift

Benign

0.20

Sift4G

Uncertain

0.057

Polyphen

0.10

Vest4

0.039

MutPred

0.26

Gain of MoRF binding (P = 0.0119);

MVP

0.076

ClinPred

0.051

GERP RS

2.8

Varity_R

0.057

gMVP

0.015

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