20-3471189-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_139321.3(ATRN):c.82G>T(p.Gly28Trp) 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. 13/21 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: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ATRN NM_139321.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.12

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

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=0.14968169).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ATRN	NM_139321.3	c.82G>T	p.Gly28Trp	missense_variant	1/29	ENST00000262919.10
ATRN	NM_001323332.2	c.82G>T	p.Gly28Trp	missense_variant	1/26
ATRN	NM_139322.4	c.82G>T	p.Gly28Trp	missense_variant	1/25
ATRN	NM_001207047.3	c.62+55G>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ATRN	ENST00000262919.10	c.82G>T	p.Gly28Trp	missense_variant	1/29	5	NM_139321.3	P2
ATRN	ENST00000446916.2	c.82G>T	p.Gly28Trp	missense_variant	1/25	1		A2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1350036 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 665648

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

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 12, 2024

The c.82G>T (p.G28W) alteration is located in exon 1 (coding exon 1) of the ATRN gene. This alteration results from a G to T substitution at nucleotide position 82, causing the glycine (G) at amino acid position 28 to be replaced by a tryptophan (W). 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	0.16
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.60
Cadd	Benign	22
Dann	Benign	0.76
DEOGEN2	Benign	0.063	T;.
Eigen	Benign	-0.82
Eigen_PC	Benign	-0.71
FATHMM_MKL	Benign	0.65	D
LIST_S2	Benign	0.46	T;T
M_CAP	Pathogenic	0.52	D
MetaRNN	Benign	0.15	T;T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	-0.34	N;N
MutationTaster	Benign	1.0	N;N
PrimateAI	Pathogenic	0.82	D
PROVEAN	Benign	-0.29	N;N
REVEL	Benign	0.098
Sift	Benign	0.040	D;D
Sift4G	Benign	0.14	T;T
Polyphen		0.0	B;B
Vest4		0.35
MutPred		0.37		Loss of methylation at R25 (P = 0.0249);Loss of methylation at R25 (P = 0.0249);
MVP		0.10
MPC		0.86
ClinPred		0.13	T
GERP RS		0.55
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.7
Varity_R		0.081
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

Other links and lift over

dbSNP: rs2084413488; hg19: chr20-3451836;