Variant rs61731845 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_001145028.2(PALM3):c.760G>A(p.Glu254Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00268 in 1,549,352 control chromosomes in the GnomAD database, including 78 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.013 ( 40 hom., cov: 32)

Exomes 𝑓: 0.0015 ( 38 hom. )

Consequence

PALM3
NM_001145028.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.926

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 Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0033938289).

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0133 (2020/152316) while in subpopulation AFR AF= 0.0451 (1874/41564). AF 95% confidence interval is 0.0434. There are 40 homozygotes in gnomad4. There are 972 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 40 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PALM3	NM_001145028.2 linkuse as main transcript	c.760G>A	p.Glu254Lys	missense_variant	7/7	ENST00000669674.2	NP_001138500.2	A6NDB9
PALM3	NM_001367327.1 linkuse as main transcript	c.562G>A	p.Glu188Lys	missense_variant	5/5		NP_001354256.1
PALM3	XM_047438763.1 linkuse as main transcript	c.679G>A	p.Glu227Lys	missense_variant	6/6		XP_047294719.1
PALM3	XM_047438764.1 linkuse as main transcript	c.562G>A	p.Glu188Lys	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.760G>A	p.Glu254Lys	missense_variant	7/7		NM_001145028.2	ENSP00000499271.1	A0A590UJ36
PALM3	ENST00000340790.9 linkuse as main transcript	c.715G>A	p.Glu239Lys	missense_variant	6/6	5		ENSP00000344996.3	A6NDB9
PALM3	ENST00000661591.1 linkuse as main transcript	c.640G>A	p.Glu214Lys	missense_variant	4/4			ENSP00000499248.1	A0A590UJ23
PALM3	ENST00000589048.2 linkuse as main transcript	c.562G>A	p.Glu188Lys	missense_variant	5/5	3		ENSP00000465701.2	K7EKN5

Frequencies

GnomAD3 genomes

AF:

0.0132

AC:

2011

AN:

152198

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0450

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00680

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.0000941

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000206

Gnomad OTH

AF:

0.0119

GnomAD3 exomes

AF:

0.00332

AC:

512

AN:

154318

Hom.:

AF XY:

0.00256

AC XY:

210

AN XY:

81978

show subpopulations

Gnomad AFR exome

AF:

0.0469

Gnomad AMR exome

AF:

0.00382

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000440

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000249

Gnomad OTH exome

AF:

0.00687

GnomAD4 exome

AF:

0.00153

AC:

2135

AN:

1397036

Hom.:

Cov.:

AF XY:

0.00133

AC XY:

918

AN XY:

689202

show subpopulations

Gnomad4 AFR exome

AF:

0.0480

Gnomad4 AMR exome

AF:

0.00443

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000560

Gnomad4 SAS exome

AF:

0.000101

Gnomad4 FIN exome

AF:

0.0000425

Gnomad4 NFE exome

AF:

0.000205

Gnomad4 OTH exome

AF:

0.00355

GnomAD4 genome

AF:

0.0133

AC:

2020

AN:

152316

Hom.:

Cov.:

AF XY:

0.0131

AC XY:

972

AN XY:

74480

show subpopulations

Gnomad4 AFR

AF:

0.0451

Gnomad4 AMR

AF:

0.00679

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000941

Gnomad4 NFE

AF:

0.000206

Gnomad4 OTH

AF:

0.0118

Alfa

AF:

0.00254

Hom.:

Bravo

AF:

0.0152

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.0405

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00414

AC:

129

Asia WGS

AF:

0.00375

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.55

CADD

Uncertain

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.013

T;T

Eigen

Uncertain

0.25

Eigen_PC

Benign

0.18

FATHMM_MKL

Benign

0.75

LIST_S2

Benign

0.83

T;.

MetaRNN

Benign

0.0034

T;T

MetaSVM

Benign

-1.2

MutationAssessor

Benign

1.8

L;.

PrimateAI

Uncertain

0.56

PROVEAN

Benign

-2.1

N;.

REVEL

Benign

0.080

Sift

Uncertain

0.0050

D;.

Sift4G

Benign

0.10

T;D

Polyphen

1.0

D;.

Vest4

0.41

MVP

0.061

ClinPred

0.032

GERP RS

3.7

Varity_R

0.24

gMVP

0.16

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over