Genetic Variant ATRN:p.Pro59Leu (chr20-3471283-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_139321.3(ATRN):c.176C>T(p.Pro59Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P59Q) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

ATRN
NM_139321.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.281

Publications

0 publications found

Variant links:

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]

ATRN links:

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ACMG classification

Classification was made for transcript

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=0.075015515).

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ATRN	NM_139321.3	MANE Select	c.176C>T	p.Pro59Leu	missense	Exon 1 of 29	NP_647537.1	O75882-1
ATRN	NM_001323332.2		c.176C>T	p.Pro59Leu	missense	Exon 1 of 26	NP_001310261.1
ATRN	NM_139322.4		c.176C>T	p.Pro59Leu	missense	Exon 1 of 25	NP_647538.1	O75882-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ATRN	ENST00000262919.10	TSL:5 MANE Select	c.176C>T	p.Pro59Leu	missense	Exon 1 of 29	ENSP00000262919.5	O75882-1
ATRN	ENST00000446916.2	TSL:1	c.176C>T	p.Pro59Leu	missense	Exon 1 of 25	ENSP00000416587.2	O75882-2
ATRN	ENST00000928835.1		c.176C>T	p.Pro59Leu	missense	Exon 1 of 28	ENSP00000598894.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1315276

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

647408

African (AFR)

AF:

0.00

AC:

AN:

26438

American (AMR)

AF:

0.00

AC:

AN:

25078

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

22128

East Asian (EAS)

AF:

0.00

AC:

AN:

29130

South Asian (SAS)

AF:

0.00

AC:

AN:

70154

European-Finnish (FIN)

AF:

0.00

AC:

AN:

33000

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3994

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1050610

Other (OTH)

AF:

0.00

AC:

AN:

54744

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.19

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.64

CADD

Benign

(source)

DANN

Benign

0.93

DEOGEN2

Benign

0.071

Eigen

Benign

-0.93

Eigen_PC

Benign

-0.90

FATHMM_MKL

Benign

0.36

LIST_S2

Benign

0.61

M_CAP

Benign

0.055

MetaRNN

Benign

0.075

MetaSVM

Benign

-0.98

MutationAssessor

Benign

0.69

PhyloP100

0.28

PrimateAI

Pathogenic

0.84

PROVEAN

Benign

-0.67

REVEL

Benign

0.029

Sift

Benign

0.30

Sift4G

Benign

0.66

Polyphen

0.0

Vest4

0.16

MutPred

0.23

Loss of glycosylation at P59 (P = 0.0207)

MVP

0.17

MPC

0.75

ClinPred

0.12

GERP RS

-1.4

PromoterAI

-0.031

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.3

Varity_R

0.032

gMVP

0.36

Mutation Taster

=93/7

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over