NM_139321.3:c.8C>T

Variant names:

• chr20-3471115-C-T
• rs1487596786
• NM_139321.3:c.8C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_139321.3(ATRN):​c.8C>T​(p.Ala3Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000736 in 1,358,338 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.4e-7 (0 hom.)
• Consequence: ATRN NM_139321.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.362
• 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 -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.066030085).

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.8C>T	p.Ala3Val	missense	Exon 1 of 29	NP_647537.1	O75882-1
	ATRN	NM_001323332.2		c.8C>T	p.Ala3Val	missense	Exon 1 of 26	NP_001310261.1
	ATRN	NM_139322.4		c.8C>T	p.Ala3Val	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.8C>T	p.Ala3Val	missense	Exon 1 of 29	ENSP00000262919.5	O75882-1
	ATRN	ENST00000446916.2	TSL:1	c.8C>T	p.Ala3Val	missense	Exon 1 of 25	ENSP00000416587.2	O75882-2
	ATRN	ENST00000928835.1		c.8C>T	p.Ala3Val	missense	Exon 1 of 28	ENSP00000598894.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000930 AC: 1 AN: 107488 AF XY: 0.0000167

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000256

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 7.36e-7 AC: 1 AN: 1358338 Hom.: 0 Cov.: 33 AF XY: 0.00000149 AC XY: 1 AN XY: 670288

African (AFR) AF: 0.00 AC: 0 AN: 28292

American (AMR) AF: 0.00 AC: 0 AN: 33964

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24234

East Asian (EAS) AF: 0.00 AC: 0 AN: 32366

South Asian (SAS) AF: 0.00 AC: 0 AN: 77500

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33288

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3996

European-Non Finnish (NFE) AF: 9.36e-7 AC: 1 AN: 1068016

Other (OTH) AF: 0.00 AC: 0 AN: 56682

GnomAD4 genome Cov.: 33

Alfa AF: 0.0000936 Hom.: 0

Bravo AF: 0.00000378

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	0.32
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	17
DANN	Uncertain	0.98
DEOGEN2	Benign	0.058	T
Eigen	Benign	-0.43
Eigen_PC	Benign	-0.36
FATHMM_MKL	Benign	0.58	D
LIST_S2	Benign	0.51	T
M_CAP	Uncertain	0.14	D
MetaRNN	Benign	0.066	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.69	N
PhyloP100		-0.36
PrimateAI	Pathogenic	0.88	D
PROVEAN	Benign	-0.060	N
REVEL	Benign	0.014
Sift	Benign	0.16	T
Sift4G	Pathogenic	0.0	D
Polyphen		0.0010	B
Vest4		0.10
MutPred		0.29		Gain of catalytic residue at A3 (P = 0.0291)
MVP		0.18
MPC		0.73
ClinPred		0.079	T
GERP RS		2.1
PromoterAI		-0.11	Neutral
Varity_R		0.035
gMVP		0.20
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: rs1487596786; hg19: chr20-3451762;