5-36260848-C-T

Variant names:

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

Variant summary

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

The NM_145000.5(RANBP3L):​c.601G>A​(p.Asp201Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000737 in 1,356,192 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.4e-7 (0 hom.)
• Consequence: RANBP3L NM_145000.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• 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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_145000.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RANBP3L	NM_145000.5	MANE Select	c.601G>A	p.Asp201Asn	missense	Exon 8 of 14	NP_659437.3
	RANBP3L	NM_001323273.2		c.601G>A	p.Asp201Asn	missense	Exon 8 of 14	NP_001310202.1
	RANBP3L	NM_001161429.3		c.676G>A	p.Asp226Asn	missense	Exon 9 of 15	NP_001154901.1	Q86VV4-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RANBP3L	ENST00000296604.8	TSL:1 MANE Select	c.601G>A	p.Asp201Asn	missense	Exon 8 of 14	ENSP00000296604.3	Q86VV4-1
	RANBP3L	ENST00000502994.5	TSL:2	c.676G>A	p.Asp226Asn	missense	Exon 9 of 15	ENSP00000421853.1	Q86VV4-3
	RANBP3L	ENST00000900326.1		c.601G>A	p.Asp201Asn	missense	Exon 8 of 14	ENSP00000570385.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.37e-7 AC: 1 AN: 1356192 Hom.: 0 Cov.: 21 AF XY: 0.00000147 AC XY: 1 AN XY: 678458

African (AFR) AF: 0.00 AC: 0 AN: 31170

American (AMR) AF: 0.00 AC: 0 AN: 42416

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24956

East Asian (EAS) AF: 0.00 AC: 0 AN: 38938

South Asian (SAS) AF: 0.0000123 AC: 1 AN: 81354

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52378

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5564

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1022888

Other (OTH) AF: 0.00 AC: 0 AN: 56528

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.077
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0013	T
Eigen	Uncertain	0.56
Eigen_PC	Uncertain	0.53
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-0.84	T
MutationAssessor	Uncertain	2.7	M
PhyloP100		2.0
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-0.45	N
REVEL	Benign	0.078
Sift	Benign	0.17	T
Sift4G	Benign	0.46	T
Polyphen		1.0	D
Vest4		0.22
MutPred		0.26		Loss of ubiquitination at K206 (P = 0.0453)
MVP		0.17
MPC		0.22
ClinPred		0.97	D
GERP RS		5.1
Varity_R		0.096
gMVP		0.26
Mutation Taster		=81/19	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.34		Details are displayed if max score is > 0.2
DS_AL_spliceai		0.34		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; COSMIC: COSV99683933; COSMIC: COSV99683933;