chr20-3471175-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_139321.3(ATRN):​c.68C>T​(p.Ala23Val) 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. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A23G) 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

1
2
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.557
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 Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.118658006).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
ATRNNM_139321.3 linkuse as main transcriptc.68C>T p.Ala23Val missense_variant 1/29 ENST00000262919.10
ATRNNM_001323332.2 linkuse as main transcriptc.68C>T p.Ala23Val missense_variant 1/26
ATRNNM_139322.4 linkuse as main transcriptc.68C>T p.Ala23Val missense_variant 1/25
ATRNNM_001207047.3 linkuse as main transcriptc.62+41C>T intron_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ATRNENST00000262919.10 linkuse as main transcriptc.68C>T p.Ala23Val missense_variant 1/295 NM_139321.3 P2O75882-1
ATRNENST00000446916.2 linkuse as main transcriptc.68C>T p.Ala23Val missense_variant 1/251 A2O75882-2

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
0.00
AC:
0
AN:
1350942
Hom.:
0
Cov.:
33
AF XY:
0.00
AC XY:
0
AN XY:
666258
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:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33

ClinVar

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

Submissions by phenotype

not provided Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingInvitaeMar 01, 2022In 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. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Not Available"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals affected with ATRN-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 23 of the ATRN protein (p.Ala23Val). -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.17
BayesDel_addAF
Benign
-0.25
T
BayesDel_noAF
Benign
-0.60
CADD
Benign
18
DANN
Uncertain
0.99
DEOGEN2
Benign
0.055
T;.
Eigen
Benign
-0.76
Eigen_PC
Benign
-0.68
FATHMM_MKL
Benign
0.30
N
LIST_S2
Benign
0.56
T;T
M_CAP
Uncertain
0.26
D
MetaRNN
Benign
0.12
T;T
MetaSVM
Benign
-0.96
T
MutationAssessor
Benign
0.69
N;N
MutationTaster
Benign
1.0
N;N
PrimateAI
Pathogenic
0.84
D
PROVEAN
Benign
0.18
N;N
REVEL
Benign
0.014
Sift
Benign
0.066
T;T
Sift4G
Benign
0.15
T;T
Polyphen
0.012
B;B
Vest4
0.12
MutPred
0.25
Loss of disorder (P = 0.1176);Loss of disorder (P = 0.1176);
MVP
0.18
MPC
0.73
ClinPred
0.091
T
GERP RS
3.0
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.085
gMVP
0.30

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr20-3451822; API