5-36261985-C-T

Variant summary

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

The NM_145000.5(RANBP3L):c.538G>A(p.Val180Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000687 in 1,455,268 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 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)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: RANBP3L NM_145000.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.240

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=0.041841745).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RANBP3L	NM_145000.5	c.538G>A	p.Val180Ile	missense_variant	7/14	ENST00000296604.8
LOC124900962	XR_007058733.1	n.127+19957C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RANBP3L	ENST00000296604.8	c.538G>A	p.Val180Ile	missense_variant	7/14	1	NM_145000.5	A2
RANBP3L	ENST00000502994.5	c.613G>A	p.Val205Ile	missense_variant	8/15	2		P4
RANBP3L	ENST00000515759.5	c.538G>A	p.Val180Ile	missense_variant	7/10	2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.87e-7 AC: 1 AN: 1455268 Hom.: 0 Cov.: 27 AF XY: 0.00000138 AC XY: 1 AN XY: 724478

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.04e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

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

Apr 22, 2022

The c.613G>A (p.V205I) alteration is located in exon 8 (coding exon 8) of the RANBP3L gene. This alteration results from a G to A substitution at nucleotide position 613, causing the valine (V) at amino acid position 205 to be replaced by an isoleucine (I). 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	0.075
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.75
Cadd	Benign	15
Dann	Benign	0.82
DEOGEN2	Benign	0.0027	T;.;.
Eigen	Benign	-0.59
Eigen_PC	Benign	-0.49
FATHMM_MKL	Benign	0.10	N
LIST_S2	Benign	0.67	T;T;T
M_CAP	Benign	0.0029	T
MetaRNN	Benign	0.042	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.73	N;.;N
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-0.21	N;N;N
REVEL	Benign	0.060
Sift	Benign	0.31	T;T;T
Sift4G	Benign	0.44	T;T;T
Polyphen		0.0060	B;.;.
Vest4		0.039
MutPred		0.20		Gain of phosphorylation at S179 (P = 0.1632);.;Gain of phosphorylation at S179 (P = 0.1632);
MVP		0.030
MPC		0.081
ClinPred		0.084	T
GERP RS		1.3
Varity_R		0.034
gMVP		0.092

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr5-36262087;