chr5-36264963-T-C

Position:

• chr5-36264963-T-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_145000.5(RANBP3L):​c.476A>G​(p.Asn159Ser) 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. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: RANBP3L NM_145000.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.257

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

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.047352195).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RANBP3L	NM_145000.5	c.476A>G	p.Asn159Ser	missense_variant	6/14	ENST00000296604.8	NP_659437.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RANBP3L	ENST00000296604.8	c.476A>G	p.Asn159Ser	missense_variant	6/14	1	NM_145000.5	ENSP00000296604.3
RANBP3L	ENST00000502994.5	c.551A>G	p.Asn184Ser	missense_variant	7/15	2		ENSP00000421853.1
RANBP3L	ENST00000515759.5	c.476A>G	p.Asn159Ser	missense_variant	6/10	2		ENSP00000421149.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

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

Sep 27, 2024

The c.551A>G (p.N184S) alteration is located in exon 7 (coding exon 7) of the RANBP3L gene. This alteration results from a A to G substitution at nucleotide position 551, causing the asparagine (N) at amino acid position 184 to be replaced by a serine (S). 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	0.068
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.77
CADD	Benign	10
DANN	Benign	0.50
DEOGEN2	Benign	0.00075	T;.;.
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.021	N
LIST_S2	Benign	0.73	T;T;T
M_CAP	Benign	0.0039	T
MetaRNN	Benign	0.047	T;T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	0.85	L;.;L
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-0.94	N;N;N
REVEL	Benign	0.046
Sift	Benign	0.45	T;T;T
Sift4G	Benign	0.74	T;T;T
Polyphen		0.0020	B;.;.
Vest4		0.029
MutPred		0.20		Gain of phosphorylation at N159 (P = 0.0563);.;Gain of phosphorylation at N159 (P = 0.0563);
MVP		0.030
MPC		0.077
ClinPred		0.12	T
GERP RS		-0.89
Varity_R		0.041
gMVP		0.083

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: chr5-36265065;