chr20-3471115-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_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. 12/21 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

Scores

2
2
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.362
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

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

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ATRNNM_139321.3 linkc.8C>T p.Ala3Val missense_variant Exon 1 of 29 ENST00000262919.10 NP_647537.1 O75882-1
ATRNNM_001323332.2 linkc.8C>T p.Ala3Val missense_variant Exon 1 of 26 NP_001310261.1 O75882
ATRNNM_139322.4 linkc.8C>T p.Ala3Val missense_variant Exon 1 of 25 NP_647538.1 O75882-2B4DZ36
ATRNNM_001207047.3 linkc.43C>T p.Leu15Leu synonymous_variant Exon 1 of 25 NP_001193976.1 O75882B4DZ36

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ATRNENST00000262919.10 linkc.8C>T p.Ala3Val missense_variant Exon 1 of 29 5 NM_139321.3 ENSP00000262919.5 O75882-1
ATRNENST00000446916.2 linkc.8C>T p.Ala3Val missense_variant Exon 1 of 25 1 ENSP00000416587.2 O75882-2

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD3 exomes
AF:
0.00000930
AC:
1
AN:
107488
Hom.:
0
AF XY:
0.0000167
AC XY:
1
AN XY:
59754
show subpopulations
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 SAS 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
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
9.36e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33
Alfa
AF:
0.0000936
Hom.:
0
Bravo
AF:
0.00000378

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Uncertain:1
Dec 04, 2024
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 3 of the ATRN protein (p.Ala3Val). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant has not been reported in the literature in individuals affected with ATRN-related conditions. An algorithm developed to predict the effect of missense changes on protein structure and function outputs the following: PolyPhen-2: "Not Available". The valine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -

Computational scores

Source: dbNSFP v4.3

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;T
M_CAP
Uncertain
0.14
D
MetaRNN
Benign
0.066
T;T
MetaSVM
Benign
-0.98
T
MutationAssessor
Benign
0.69
N;N
PrimateAI
Pathogenic
0.88
D
PROVEAN
Benign
-0.060
N;N
REVEL
Benign
0.014
Sift
Benign
0.16
T;T
Sift4G
Pathogenic
0.0
D;D
Polyphen
0.0010
B;B
Vest4
0.10
MutPred
0.29
Gain of catalytic residue at A3 (P = 0.0291);Gain of catalytic residue at A3 (P = 0.0291);
MVP
0.18
MPC
0.73
ClinPred
0.079
T
GERP RS
2.1
Varity_R
0.035
gMVP
0.20

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1487596786; hg19: chr20-3451762; API