20-3471283-C-A

Variant names:

• chr20-3471283-C-A
• rs2084416122
• NM_139321.3:c.176C>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2 BP4_Moderate BS2

The NM_139321.3(ATRN):​c.176C>A​(p.Pro59Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000038 in 1,315,278 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. P59P) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000038 (0 hom.)
• Consequence: ATRN NM_139321.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.281
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.100807935).
• BS2: High AC in GnomAdExome4 at 5 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_139321.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATRN	NM_139321.3	MANE Select	c.176C>A	p.Pro59Gln	missense	Exon 1 of 29	NP_647537.1	O75882-1
	ATRN	NM_001323332.2		c.176C>A	p.Pro59Gln	missense	Exon 1 of 26	NP_001310261.1
	ATRN	NM_139322.4		c.176C>A	p.Pro59Gln	missense	Exon 1 of 25	NP_647538.1	O75882-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATRN	ENST00000262919.10	TSL:5 MANE Select	c.176C>A	p.Pro59Gln	missense	Exon 1 of 29	ENSP00000262919.5	O75882-1
	ATRN	ENST00000446916.2	TSL:1	c.176C>A	p.Pro59Gln	missense	Exon 1 of 25	ENSP00000416587.2	O75882-2
	ATRN	ENST00000928835.1		c.176C>A	p.Pro59Gln	missense	Exon 1 of 28	ENSP00000598894.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000380 AC: 5 AN: 1315278 Hom.: 0 Cov.: 32 AF XY: 0.00000463 AC XY: 3 AN XY: 647408

African (AFR) AF: 0.00 AC: 0 AN: 26438

American (AMR) AF: 0.00 AC: 0 AN: 25078

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22128

East Asian (EAS) AF: 0.00 AC: 0 AN: 29130

South Asian (SAS) AF: 0.00 AC: 0 AN: 70154

European-Finnish (FIN) AF: 0.0000303 AC: 1 AN: 33000

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3994

European-Non Finnish (NFE) AF: 0.00000286 AC: 3 AN: 1050612

Other (OTH) AF: 0.0000183 AC: 1 AN: 54744

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	14
DANN	Benign	0.92
DEOGEN2	Benign	0.069	T
Eigen	Benign	-0.91
Eigen_PC	Benign	-0.89
FATHMM_MKL	Benign	0.49	N
LIST_S2	Benign	0.48	T
M_CAP	Benign	0.047	D
MetaRNN	Benign	0.10	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	0.69	N
PhyloP100		0.28
PrimateAI	Pathogenic	0.82	D
PROVEAN	Benign	-0.16	N
REVEL	Benign	0.027
Sift	Benign	0.12	T
Sift4G	Benign	0.28	T
Polyphen		0.018	B
Vest4		0.26
MutPred		0.22		Loss of glycosylation at P59 (P = 0.0207)
MVP		0.30
MPC		0.68
ClinPred		0.090	T
GERP RS		-1.4
PromoterAI		-0.053	Neutral
Varity_R		0.039
gMVP		0.40
Mutation Taster		=91/9	polymorphism

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

Other links and lift over

dbSNP: rs2084416122; hg19: chr20-3451930;