20-3471204-T-C

Variant names:

• chr20-3471204-T-C
• rs2084413851
• NM_139321.3:c.97T>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_139321.3(ATRN):​c.97T>C​(p.Trp33Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000658 in 152,032 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ATRN NM_139321.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.03
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.11095965).

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.97T>C	p.Trp33Arg	missense	Exon 1 of 29	NP_647537.1	O75882-1
	ATRN	NM_001323332.2		c.97T>C	p.Trp33Arg	missense	Exon 1 of 26	NP_001310261.1
	ATRN	NM_139322.4		c.97T>C	p.Trp33Arg	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.97T>C	p.Trp33Arg	missense	Exon 1 of 29	ENSP00000262919.5	O75882-1
	ATRN	ENST00000446916.2	TSL:1	c.97T>C	p.Trp33Arg	missense	Exon 1 of 25	ENSP00000416587.2	O75882-2
	ATRN	ENST00000928835.1		c.97T>C	p.Trp33Arg	missense	Exon 1 of 28	ENSP00000598894.1

Frequencies

GnomAD3 genomes AF: 0.00000658 AC: 1 AN: 152032 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1347958 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 664462

African (AFR) AF: 0.00 AC: 0 AN: 27724

American (AMR) AF: 0.00 AC: 0 AN: 32570

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23712

East Asian (EAS) AF: 0.00 AC: 0 AN: 31284

South Asian (SAS) AF: 0.00 AC: 0 AN: 75636

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33100

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3992

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1063708

Other (OTH) AF: 0.00 AC: 0 AN: 56232

GnomAD4 genome AF: 0.00000658 AC: 1 AN: 152032 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 74284

African (AFR) AF: 0.0000241 AC: 1 AN: 41416

American (AMR) AF: 0.00 AC: 0 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10586

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67970

Other (OTH) AF: 0.00 AC: 0 AN: 2084

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	14
DANN	Benign	0.83
DEOGEN2	Benign	0.066	T
Eigen	Benign	-0.84
Eigen_PC	Benign	-0.77
FATHMM_MKL	Benign	0.086	N
LIST_S2	Benign	0.34	T
M_CAP	Pathogenic	0.37	D
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	0.34	N
PhyloP100		-1.0
PrimateAI	Pathogenic	0.84	D
PROVEAN	Benign	-0.13	N
REVEL	Benign	0.020
Sift	Benign	0.058	T
Sift4G	Pathogenic	0.0	D
Polyphen		0.0	B
Vest4		0.18
MutPred		0.36		Gain of MoRF binding (P = 0.0654)
MVP		0.068
MPC		1.3
ClinPred		0.17	T
GERP RS		0.98
PromoterAI		0.0080	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.12
gMVP		0.19
Mutation Taster		=89/11	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: rs2084413851; hg19: chr20-3451851;