11-57476594-A-C

Variant names:

• chr11-57476594-A-C
• NM_178570.3:c.946A>C

Variant summary

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

The NM_178570.3(RTN4RL2):​c.946A>C​(p.Thr316Pro) 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. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: RTN4RL2 NM_178570.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.81

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]

ENSG00000255301 (HGNC:):

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=0.20889464).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RTN4RL2	NM_178570.3	c.946A>C	p.Thr316Pro	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.946A>C	p.Thr316Pro	missense_variant	Exon 3 of 3	1	NM_178570.3	ENSP00000335397.3
ENSG00000255301	ENST00000528885.1	n.583T>G		non_coding_transcript_exon_variant	Exon 2 of 2	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jun 18, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.946A>C (p.T316P) alteration is located in exon 3 (coding exon 3) of the RTN4RL2 gene. This alteration results from a A to C substitution at nucleotide position 946, causing the threonine (T) at amino acid position 316 to be replaced by a proline (P). 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	0.039
BayesDel_addAF	Benign	-0.098	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	16
DANN	Benign	0.91
DEOGEN2	Benign	0.049	T
Eigen	Benign	-0.49
Eigen_PC	Benign	-0.44
FATHMM_MKL	Benign	0.14	N
LIST_S2	Benign	0.42	T
M_CAP	Pathogenic	0.44	D
MetaRNN	Benign	0.21	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.55	N
PrimateAI	Pathogenic	0.91	D
PROVEAN	Benign	-0.40	N
REVEL	Benign	0.087
Sift	Benign	0.23	T
Sift4G	Benign	0.22	T
Polyphen		0.65	P
Vest4		0.25
MutPred		0.20		Gain of loop (P = 0.0097);
MVP		0.48
MPC		1.5
ClinPred		0.23	T
GERP RS		3.9
Varity_R		0.25
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: chr11-57244067;