5-36251422-C-G

Variant names:

• chr5-36251422-C-G
• NM_145000.5:c.1245G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_145000.5(RANBP3L):​c.1245G>C​(p.Gln415His) 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. 14/22 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)
• Consequence: RANBP3L NM_145000.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.788
• Publications: 0 publications found

Genes affected

RANBP3L (HGNC:26353): (RAN binding protein 3 like) Enables SMAD binding activity. Predicted to be involved in several processes, including mesenchymal cell differentiation involved in bone development; negative regulation of osteoblast differentiation; and positive regulation of myoblast differentiation. Predicted to be part of nuclear pore. Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

LOC124900962 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08515912).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RANBP3L	NM_145000.5	c.1245G>C	p.Gln415His	missense_variant	Exon 13 of 14	ENST00000296604.8	NP_659437.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RANBP3L	ENST00000296604.8	c.1245G>C	p.Gln415His	missense_variant	Exon 13 of 14	1	NM_145000.5	ENSP00000296604.3
RANBP3L	ENST00000502994.5	c.1320G>C	p.Gln440His	missense_variant	Exon 14 of 15	2		ENSP00000421853.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jun 09, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1320G>C (p.Q440H) alteration is located in exon 14 (coding exon 14) of the RANBP3L gene. This alteration results from a G to C substitution at nucleotide position 1320, causing the glutamine (Q) at amino acid position 440 to be replaced by a histidine (H). 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	0.18
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	15
DANN	Benign	0.96
DEOGEN2	Benign	0.010	T;.
Eigen	Benign	-0.54
Eigen_PC	Benign	-0.56
FATHMM_MKL	Uncertain	0.79	D
LIST_S2	Benign	0.61	T;T
M_CAP	Benign	0.0052	T
MetaRNN	Benign	0.085	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.1	M;.
PhyloP100		0.79
PrimateAI	Benign	0.31	T
PROVEAN	Uncertain	-2.5	D;D
REVEL	Benign	0.091
Sift	Benign	0.057	T;T
Sift4G	Uncertain	0.052	T;T
Polyphen		0.34	B;.
Vest4		0.24
MutPred		0.25		Loss of methylation at K414 (P = 0.1098);.;
MVP		0.040
MPC		0.096
ClinPred		0.20	T
GERP RS		0.74
Varity_R		0.089
gMVP		0.18
Mutation Taster		=87/13	polymorphism

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

Other links and lift over

hg19: chr5-36251524;