rs3886999

Positions:

• chr20-3596415-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 5.79

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]

ACMG classification

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	UniProt
ATRN	NM_139321.3	c.3455G>A	p.Arg1152Lys	missense_variant	21/29	ENST00000262919.10	NP_647537.1
ATRN	NM_001323332.2	c.3455G>A	p.Arg1152Lys	missense_variant	21/26		NP_001310261.1
ATRN	NM_139322.4	c.3455G>A	p.Arg1152Lys	missense_variant	21/25		NP_647538.1
ATRN	NM_001207047.3	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	c.3455G>A	p.Arg1152Lys	missense_variant	21/29	5	NM_139321.3	ENSP00000262919	P2
ATRN	ENST00000446916.2	c.3455G>A	p.Arg1152Lys	missense_variant	21/25	1		ENSP00000416587	A2

Frequencies

GnomAD3 genomes AF: 0.0382 AC: 5812 AN: 152184 Hom.: 148 Cov.: 32

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

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.: 31 AF XY: 0.0479 AC XY: 34843 AN XY: 726770

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.: 32 AF XY: 0.0379 AC XY: 2821 AN XY: 74464

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: 45

ESP6500EA AF: 0.0562 AC: 483

ExAC AF: 0.0389 AC: 4718

Asia WGS AF: 0.0140 AC: 49 AN: 3478

EpiCase AF: 0.0553

EpiControl AF: 0.0584

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

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	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	19
DANN	Benign	0.80
DEOGEN2	Benign	0.061	T;.
Eigen	Benign	-0.39
Eigen_PC	Benign	-0.15
FATHMM_MKL	Benign	0.039	N
LIST_S2	Benign	0.39	T;T
MetaRNN	Benign	0.0050	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.28	N;N
MutationTaster	Benign	1.0	N;N
PrimateAI	Pathogenic	0.89	D
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	T
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

Other links and lift over

dbSNP: rs3886999; hg19: chr20-3577062;