rs2111749444

Variant names:

• chr5-36260848-C-G
• rs2111749444
• NM_145000.5:c.601G>C

Your query was ambiguous. Multiple possible variants found:

• chr5-36260848-C-G
• chr5-36260848-C-T

Variant summary

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

The NM_145000.5(RANBP3L):​c.601G>C​(p.Asp201His) 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. 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. D201N) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: RANBP3L NM_145000.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.04
• 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.601G>C	p.Asp201His	missense_variant	Exon 8 of 14	ENST00000296604.8	NP_659437.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RANBP3L	ENST00000296604.8	c.601G>C	p.Asp201His	missense_variant	Exon 8 of 14	1	NM_145000.5	ENSP00000296604.3
RANBP3L	ENST00000502994.5	c.676G>C	p.Asp226His	missense_variant	Exon 9 of 15	2		ENSP00000421853.1
RANBP3L	ENST00000515759.5	c.601G>C	p.Asp201His	missense_variant	Exon 8 of 10	2		ENSP00000421149.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 21

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.096	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.080	T;.;.
Eigen	Uncertain	0.64
Eigen_PC	Uncertain	0.59
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.85	T;T;T
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.21	T;T;T
MetaSVM	Benign	-0.82	T
MutationAssessor	Uncertain	2.7	M;.;M
PhyloP100		2.0
PrimateAI	Benign	0.41	T
PROVEAN	Benign	-2.3	N;N;N
REVEL	Benign	0.078
Sift	Uncertain	0.0050	D;D;D
Sift4G	Uncertain	0.026	D;D;D
Polyphen		1.0	D;.;.
Vest4		0.29
MutPred		0.28		Loss of ubiquitination at K206 (P = 0.0584);.;Loss of ubiquitination at K206 (P = 0.0584);
MVP		0.27
MPC		0.52
ClinPred		0.93	D
GERP RS		5.1
Varity_R		0.17
gMVP		0.38
Mutation Taster		=80/20	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.30		Details are displayed if max score is > 0.2
DS_AL_spliceai		0.30		Position offset: 16

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2111749444; hg19: chr5-36260950;