chr20-3471175-C-G

Variant summary

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

The NM_139321.3(ATRN):​c.68C>G​(p.Ala23Gly) 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. A23V) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

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]

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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=0.11037591).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
ATRNNM_139321.3 linkuse as main transcriptc.68C>G p.Ala23Gly missense_variant 1/29 ENST00000262919.10
ATRNNM_001323332.2 linkuse as main transcriptc.68C>G p.Ala23Gly missense_variant 1/26
ATRNNM_139322.4 linkuse as main transcriptc.68C>G p.Ala23Gly missense_variant 1/25
ATRNNM_001207047.3 linkuse as main transcriptc.62+41C>G intron_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ATRNENST00000262919.10 linkuse as main transcriptc.68C>G p.Ala23Gly missense_variant 1/295 NM_139321.3 P2O75882-1
ATRNENST00000446916.2 linkuse as main transcriptc.68C>G p.Ala23Gly missense_variant 1/251 A2O75882-2

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
33
GnomAD4 genome
Cov.:
33

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsJul 20, 2021The c.68C>G (p.A23G) alteration is located in exon 1 (coding exon 1) of the ATRN gene. This alteration results from a C to G substitution at nucleotide position 68, causing the alanine (A) at amino acid position 23 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.077
BayesDel_addAF
Benign
-0.24
T
BayesDel_noAF
Benign
-0.58
CADD
Benign
17
DANN
Uncertain
0.98
DEOGEN2
Benign
0.055
T;.
Eigen
Benign
-0.81
Eigen_PC
Benign
-0.73
FATHMM_MKL
Benign
0.17
N
LIST_S2
Benign
0.45
T;T
M_CAP
Uncertain
0.23
D
MetaRNN
Benign
0.11
T;T
MetaSVM
Benign
-0.94
T
MutationAssessor
Benign
0.69
N;N
MutationTaster
Benign
1.0
N;N
PrimateAI
Pathogenic
0.83
D
PROVEAN
Benign
-0.080
N;N
REVEL
Benign
0.025
Sift
Benign
0.085
T;T
Sift4G
Benign
0.11
T;T
Polyphen
0.0
B;B
Vest4
0.093
MutPred
0.21
Loss of helix (P = 0.0093);Loss of helix (P = 0.0093);
MVP
0.21
MPC
0.74
ClinPred
0.066
T
GERP RS
3.0
Varity_R
0.10
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

No publications associated with this variant yet.

Other links and lift over

hg19: chr20-3451822; API