rs769922018

Variant names:

• chr11-57476175-C-A
• NM_178570.3:c.527C>A

Your query was ambiguous. Multiple possible variants found:

• chr11-57476175-C-A
• chr11-57476175-C-T

Variant summary

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

The NM_178570.3(RTN4RL2):​c.527C>A​(p.Ala176Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000206 in 1,453,750 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. 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. A176V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: RTN4RL2 NM_178570.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.636

Genes affected

RTN4RL2 (HGNC:23053): (reticulon 4 receptor like 2) Enables signaling receptor activity. Predicted to be involved in cell surface receptor signaling pathway; corpus callosum development; and negative regulation of neuron projection development. Located in cell surface. Is anchored component of plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

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=0.21683022).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RTN4RL2	NM_178570.3	c.527C>A	p.Ala176Glu	missense_variant	Exon 3 of 3	ENST00000335099.8	NP_848665.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RTN4RL2	ENST00000335099.8	c.527C>A	p.Ala176Glu	missense_variant	Exon 3 of 3	1	NM_178570.3	ENSP00000335397.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000206 AC: 3 AN: 1453750 Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1 AN XY: 722098

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: 0.0000234

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.03e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.25
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Uncertain	24
DANN	Benign	0.94
DEOGEN2	Benign	0.21	T
Eigen	Benign	-0.67
Eigen_PC	Benign	-0.70
FATHMM_MKL	Benign	0.46	N
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.029	D
MetaRNN	Benign	0.22	T
MetaSVM	Benign	-0.69	T
MutationAssessor	Benign	1.4	L
PrimateAI	Uncertain	0.69	T
PROVEAN	Uncertain	-2.7	D
REVEL	Benign	0.078
Sift	Benign	0.060	T
Sift4G	Benign	1.0	T
Polyphen		0.81	P
Vest4		0.39
MutPred		0.42		Loss of catalytic residue at A176 (P = 0.0823);
MVP		0.19
MPC		2.2
ClinPred		0.49	T
GERP RS		2.6
Varity_R		0.28
gMVP		0.60

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: chr11-57243648;