rs17782078

Positions:

• chr20-3560735-T-C

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.1277T>C​(p.Ile426Thr) variant causes a missense change. The variant allele was found at a frequency of 0.0476 in 1,613,938 control chromosomes in the GnomAD database, including 2,114 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 (146 hom., cov: 32)
  • Exomes 𝑓: 0.049 (1968 hom.)
• Consequence: ATRN NM_139321.3 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 5.99

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=0.003145665).
• BP6: Variant 20-3560735-T-C is Benign according to our data. Variant chr20-3560735-T-C is described in ClinVar as [Benign]. Clinvar id is 1167765.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0545 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATRN	NM_139321.3	c.1277T>C	p.Ile426Thr	missense_variant	8/29	ENST00000262919.10	NP_647537.1
ATRN	NM_001323332.2	c.1277T>C	p.Ile426Thr	missense_variant	8/26		NP_001310261.1
ATRN	NM_139322.4	c.1277T>C	p.Ile426Thr	missense_variant	8/25		NP_647538.1
ATRN	NM_001207047.3	c.929T>C	p.Ile310Thr	missense_variant	8/25		NP_001193976.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ATRN	ENST00000262919.10	c.1277T>C	p.Ile426Thr	missense_variant	8/29	5	NM_139321.3	ENSP00000262919.5
ATRN	ENST00000446916.2	c.1277T>C	p.Ile426Thr	missense_variant	8/25	1		ENSP00000416587.2

Frequencies

GnomAD3 genomes AF: 0.0380 AC: 5783 AN: 152134 Hom.: 146 Cov.: 32

Gnomad AFR AF: 0.00936

Gnomad AMI AF: 0.0855

Gnomad AMR AF: 0.0406

Gnomad ASJ AF: 0.0274

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0106

Gnomad FIN AF: 0.0609

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.0560

Gnomad OTH AF: 0.0406

GnomAD3 exomes AF: 0.0393 AC: 9871 AN: 251290 Hom.: 240 AF XY: 0.0395 AC XY: 5359 AN XY: 135808

Gnomad AFR exome AF: 0.00837

Gnomad AMR exome AF: 0.0288

Gnomad ASJ exome AF: 0.0331

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0101

Gnomad FIN exome AF: 0.0684

Gnomad NFE exome AF: 0.0559

Gnomad OTH exome AF: 0.0440

GnomAD4 exome AF: 0.0487 AC: 71114 AN: 1461686 Hom.: 1968 Cov.: 32 AF XY: 0.0478 AC XY: 34757 AN XY: 727156

Gnomad4 AFR exome AF: 0.00824

Gnomad4 AMR exome AF: 0.0297

Gnomad4 ASJ exome AF: 0.0337

Gnomad4 EAS exome AF: 0.0000756

Gnomad4 SAS exome AF: 0.00976

Gnomad4 FIN exome AF: 0.0688

Gnomad4 NFE exome AF: 0.0553

Gnomad4 OTH exome AF: 0.0422

GnomAD4 genome AF: 0.0380 AC: 5781 AN: 152252 Hom.: 146 Cov.: 32 AF XY: 0.0376 AC XY: 2799 AN XY: 74444

Gnomad4 AFR AF: 0.00934

Gnomad4 AMR AF: 0.0405

Gnomad4 ASJ AF: 0.0274

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.0106

Gnomad4 FIN AF: 0.0609

Gnomad4 NFE AF: 0.0560

Gnomad4 OTH AF: 0.0402

Alfa AF: 0.0512 Hom.: 457

Bravo AF: 0.0354

TwinsUK AF: 0.0545 AC: 202

ALSPAC AF: 0.0610 AC: 235

ESP6500AA AF: 0.0102 AC: 45

ESP6500EA AF: 0.0563 AC: 484

ExAC AF: 0.0387 AC: 4694

Asia WGS AF: 0.00722 AC: 25 AN: 3478

EpiCase AF: 0.0556

EpiControl AF: 0.0586

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jan 15, 2021	- -
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	0.23
BayesDel_addAF	Benign	-0.42	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	21
DANN	Benign	0.97
DEOGEN2	Benign	0.22	T;.
Eigen	Benign	-0.072
Eigen_PC	Benign	0.12
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Uncertain	0.93	D;D
MetaRNN	Benign	0.0031	T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.89	L;L
PrimateAI	Uncertain	0.78	T
PROVEAN	Uncertain	-2.5	D;N
REVEL	Benign	0.14
Sift	Benign	0.16	T;T
Sift4G	Benign	0.32	T;T
Polyphen		0.080	B;B
Vest4		0.18
MPC		0.20
ClinPred		0.014	T
GERP RS		5.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.29
gMVP		0.83

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

Other links and lift over

dbSNP: rs17782078; hg19: chr20-3541382;