chr20-3596415-G-A

Position:

chr20-3596415-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_139321.3(ATRN):c.3455G>A(p.Arg1152Lys) variant causes a missense change. The variant allele was found at a frequency of 0.0477 in 1,613,122 control chromosomes in the GnomAD database, including 2,117 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.038 ( 148 hom., cov: 32)

Exomes 𝑓: 0.049 ( 1969 hom. )

Consequence

ATRN
NM_139321.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 5.79

Variant links:

Genes affected

ATRN (HGNC:885): (attractin) This gene encodes both membrane-bound and secreted protein isoforms. A membrane-bound isoform exhibits sequence similarity with the mouse mahogany protein, a receptor involved in controlling obesity. A secreted isoform is involved in the initial immune cell clustering during inflammatory responses that may regulate the chemotactic activity of chemokines. [provided by RefSeq, Apr 2016]

ATRN links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0049655437).

BP6

Variant 20-3596415-G-A is Benign according to our data. Variant chr20-3596415-G-A is described in ClinVar as [Benign]. Clinvar id is 1167767.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0546 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
ATRN	NM_139321.3 linkuse as main transcript	c.3455G>A	p.Arg1152Lys	missense_variant	21/29	ENST00000262919.10	NP_647537.1
ATRN	NM_001323332.2 linkuse as main transcript	c.3455G>A	p.Arg1152Lys	missense_variant	21/26		NP_001310261.1
ATRN	NM_139322.4 linkuse as main transcript	c.3455G>A	p.Arg1152Lys	missense_variant	21/25		NP_647538.1
ATRN	NM_001207047.3 linkuse as main transcript	c.3107G>A	p.Arg1036Lys	missense_variant	21/25		NP_001193976.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ATRN	ENST00000262919.10 linkuse as main transcript	c.3455G>A	p.Arg1152Lys	missense_variant	21/29	5	NM_139321.3	ENSP00000262919	P2	O75882-1
ATRN	ENST00000446916.2 linkuse as main transcript	c.3455G>A	p.Arg1152Lys	missense_variant	21/25	1		ENSP00000416587	A2	O75882-2

Frequencies

GnomAD3 genomes

AF:

0.0382

AC:

5812

AN:

152184

Hom.:

148

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00934

Gnomad AMI

AF:

0.0855

Gnomad AMR

AF:

0.0406

Gnomad ASJ

AF:

0.0274

Gnomad EAS

AF:

0.00173

Gnomad SAS

AF:

0.0132

Gnomad FIN

AF:

0.0610

Gnomad MID

AF:

0.0285

Gnomad NFE

AF:

0.0561

Gnomad OTH

AF:

0.0406

GnomAD3 exomes

AF:

0.0394

AC:

9883

AN:

251052

Hom.:

242

AF XY:

0.0397

AC XY:

5380

AN XY:

135680

show subpopulations

Gnomad AFR exome

AF:

0.00831

Gnomad AMR exome

AF:

0.0285

Gnomad ASJ exome

AF:

0.0333

Gnomad EAS exome

AF:

0.000707

Gnomad SAS exome

AF:

0.0115

Gnomad FIN exome

AF:

0.0683

Gnomad NFE exome

AF:

0.0557

Gnomad OTH exome

AF:

0.0443

GnomAD4 exome

AF:

0.0487

AC:

71191

AN:

1460820

Hom.:

1969

Cov.:

AF XY:

0.0479

AC XY:

34843

AN XY:

726770

show subpopulations

Gnomad4 AFR exome

AF:

0.00822

Gnomad4 AMR exome

AF:

0.0295

Gnomad4 ASJ exome

AF:

0.0335

Gnomad4 EAS exome

AF:

0.00527

Gnomad4 SAS exome

AF:

0.0113

Gnomad4 FIN exome

AF:

0.0687

Gnomad4 NFE exome

AF:

0.0551

Gnomad4 OTH exome

AF:

0.0424

GnomAD4 genome

AF:

0.0382

AC:

5812

AN:

152302

Hom.:

148

Cov.:

AF XY:

0.0379

AC XY:

2821

AN XY:

74464

show subpopulations

Gnomad4 AFR

AF:

0.00931

Gnomad4 AMR

AF:

0.0406

Gnomad4 ASJ

AF:

0.0274

Gnomad4 EAS

AF:

0.00173

Gnomad4 SAS

AF:

0.0135

Gnomad4 FIN

AF:

0.0610

Gnomad4 NFE

AF:

0.0561

Gnomad4 OTH

AF:

0.0402

Alfa

AF:

0.0510

Hom.:

536

Bravo

AF:

0.0354

TwinsUK

AF:

0.0545

AC:

202

ALSPAC

AF:

0.0612

AC:

236

ESP6500AA

AF:

0.0102

AC:

ESP6500EA

AF:

0.0562

AC:

483

ExAC

AF:

0.0389

AC:

4718

Asia WGS

AF:

0.0140

AC:

AN:

3478

EpiCase

AF:

0.0553

EpiControl

AF:

0.0584

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 25, 2024	- -

ATRN-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jul 29, 2024

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.059

BayesDel_addAF

Benign

-0.63

BayesDel_noAF

Benign

-0.64

CADD

Benign

DANN

Benign

0.80

DEOGEN2

Benign

0.061

T;.

Eigen

Benign

-0.39

Eigen_PC

Benign

-0.15

FATHMM_MKL

Benign

0.039

LIST_S2

Benign

0.39

T;T

MetaRNN

Benign

0.0050

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.28

N;N

MutationTaster

Benign

1.0

N;N

PrimateAI

Pathogenic

0.89

PROVEAN

Benign

-0.23

N;N

REVEL

Benign

0.11

Sift

Benign

1.0

T;T

Sift4G

Benign

0.87

T;T

Polyphen

0.0

B;B

Vest4

0.053

MPC

0.53

ClinPred

0.029

GERP RS

6.0

Varity_R

0.079

gMVP

0.22

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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