rs904536484

Variant names:

• chr5-36256984-A-C
• rs904536484
• NM_145000.5:c.860T>G

Your query was ambiguous. Multiple possible variants found:

• chr5-36256984-A-C
• chr5-36256984-A-G

Variant summary

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

The NM_145000.5(RANBP3L):​c.860T>G​(p.Ile287Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,460,996 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. I287T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: RANBP3L NM_145000.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.99
• 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RANBP3L	NM_145000.5	c.860T>G	p.Ile287Ser	missense_variant	Exon 10 of 14	ENST00000296604.8	NP_659437.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RANBP3L	ENST00000296604.8	c.860T>G	p.Ile287Ser	missense_variant	Exon 10 of 14	1	NM_145000.5	ENSP00000296604.3
RANBP3L	ENST00000502994.5	c.935T>G	p.Ile312Ser	missense_variant	Exon 11 of 15	2		ENSP00000421853.1
RANBP3L	ENST00000515759.5	c.860T>G	p.Ile287Ser	missense_variant	Exon 10 of 10	2		ENSP00000421149.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1460996 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 726804

African (AFR) AF: 0.00 AC: 0 AN: 33442

American (AMR) AF: 0.00 AC: 0 AN: 44704

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26118

East Asian (EAS) AF: 0.00 AC: 0 AN: 39618

South Asian (SAS) AF: 0.00 AC: 0 AN: 86162

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53396

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1111430

Other (OTH) AF: 0.00 AC: 0 AN: 60362

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.24
BayesDel_addAF	Benign	-0.044	T
BayesDel_noAF	Benign	-0.30
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.20	T;.;.
Eigen	Benign	-0.076
Eigen_PC	Benign	0.034
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.72	T;D;D
M_CAP	Benign	0.0083	T
MetaRNN	Uncertain	0.51	D;D;D
MetaSVM	Benign	-0.98	T
MutationAssessor	Uncertain	2.1	M;.;M
PhyloP100		5.0
PrimateAI	Benign	0.47	T
PROVEAN	Pathogenic	-5.1	D;D;D
REVEL	Benign	0.17
Sift	Uncertain	0.010	D;D;D
Sift4G	Benign	0.097	T;T;T
Polyphen		0.18	B;.;.
Vest4		0.53
MutPred		0.56		Loss of stability (P = 0.0038);.;Loss of stability (P = 0.0038);
MVP		0.45
MPC		0.24
ClinPred		0.92	D
GERP RS		4.3
Varity_R		0.57
gMVP		0.44
Mutation Taster		=80/20	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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

dbSNP: rs904536484; hg19: chr5-36257086;