Variant 19-14053615-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001145028.2(PALM3):c.2057C>T(p.Ala686Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000241 in 1,456,422 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00017 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00025 ( 2 hom. )

Consequence

PALM3
NM_001145028.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.343

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 -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0077739954).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
PALM3	NM_001145028.2 linkuse as main transcript	c.2057C>T	p.Ala686Val	missense_variant	7/7	ENST00000669674.2
PALM3	NM_001367327.1 linkuse as main transcript	c.1859C>T	p.Ala620Val	missense_variant	5/5
PALM3	XM_047438763.1 linkuse as main transcript	c.1976C>T	p.Ala659Val	missense_variant	6/6
PALM3	XM_047438764.1 linkuse as main transcript	c.1859C>T	p.Ala620Val	missense_variant	5/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
PALM3	ENST00000669674.2 linkuse as main transcript	c.2057C>T	p.Ala686Val	missense_variant	7/7		NM_001145028.2	A2
PALM3	ENST00000340790.9 linkuse as main transcript	c.2012C>T	p.Ala671Val	missense_variant	6/6	5		P4
PALM3	ENST00000661591.1 linkuse as main transcript	c.1937C>T	p.Ala646Val	missense_variant	4/4			A2
PALM3	ENST00000589048.2 linkuse as main transcript	c.1859C>T	p.Ala620Val	missense_variant	5/5	3		A2

Frequencies

GnomAD3 genomes

AF:

0.000164

AC:

AN:

152158

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00145

Gnomad FIN

AF:

0.0000942

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000206

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000389

AC:

AN:

79642

Hom.:

AF XY:

0.000439

AC XY:

AN XY:

38726

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:

0.00234

Gnomad FIN exome

AF:

0.0000940

Gnomad NFE exome

AF:

0.000402

Gnomad OTH exome

AF:

0.000894

GnomAD4 exome

AF:

0.000249

AC:

325

AN:

1304146

Hom.:

Cov.:

AF XY:

0.000289

AC XY:

183

AN XY:

632860

show subpopulations

Gnomad4 AFR exome

AF:

0.000106

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00191

Gnomad4 FIN exome

AF:

0.0000656

Gnomad4 NFE exome

AF:

0.000161

Gnomad4 OTH exome

AF:

0.000353

GnomAD4 genome

AF:

0.000171

AC:

AN:

152276

Hom.:

Cov.:

AF XY:

0.000175

AC XY:

AN XY:

74444

show subpopulations

Gnomad4 AFR

AF:

0.0000722

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00166

Gnomad4 FIN

AF:

0.0000942

Gnomad4 NFE

AF:

0.000206

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000121

Hom.:

Bravo

AF:

0.000162

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000629

AC:

ExAC

AF:

0.000526

AC:

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

Jun 17, 2022

The c.2012C>T (p.A671V) 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 2012, causing the alanine (A) at amino acid position 671 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

0.13

BayesDel_addAF

Benign

-0.63

BayesDel_noAF

Benign

-0.68

Cadd

Benign

2.9

Dann

Benign

0.96

DEOGEN2

Benign

0.0016

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.052

LIST_S2

Benign

0.57

MetaRNN

Benign

0.0078

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.72

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.49

PROVEAN

Benign

-0.67

REVEL

Benign

0.015

Sift

Benign

0.42

Sift4G

Benign

0.69

Polyphen

0.37

Vest4

0.14

MVP

0.014

ClinPred

0.010

GERP RS

-1.3

Varity_R

0.034

gMVP

0.072

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