5-36269453-G-A

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_145000.5(RANBP3L):c.205C>T(p.Pro69Ser) 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. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: RANBP3L NM_145000.5 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.18

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 -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.025699228).
• BP6: Variant 5-36269453-G-A is Benign according to our data. Variant chr5-36269453-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2534913.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RANBP3L	NM_145000.5	c.205C>T	p.Pro69Ser	missense_variant	4/14	ENST00000296604.8
LOC124900962	XR_007058733.1	n.127+27425G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RANBP3L	ENST00000296604.8	c.205C>T	p.Pro69Ser	missense_variant	4/14	1	NM_145000.5	A2
RANBP3L	ENST00000502994.5	c.205C>T	p.Pro69Ser	missense_variant	4/15	2		P4
RANBP3L	ENST00000515759.5	c.205C>T	p.Pro69Ser	missense_variant	4/10	2
RANBP3L	ENST00000505865.1	c.205C>T	p.Pro69Ser	missense_variant	5/6	4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1389096 Hom.: 0 Cov.: 25 AF XY: 0.00 AC XY: 0 AN XY: 695224

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 07, 2023

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.065
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.62
Cadd	Benign	8.7
Dann	Benign	0.33
DEOGEN2	Benign	0.0017	T;.;.;.
Eigen	Benign	-0.86
Eigen_PC	Benign	-0.66
FATHMM_MKL	Benign	0.022	N
LIST_S2	Benign	0.49	T;T;T;T
M_CAP	Benign	0.0019	T
MetaRNN	Benign	0.026	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-1.2	N;N;N;.
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-0.44	N;N;N;N
REVEL	Benign	0.010
Sift	Benign	0.87	T;T;T;T
Sift4G	Benign	0.82	T;T;T;.
Polyphen		0.0	B;.;.;.
Vest4		0.034
MutPred		0.25		Gain of catalytic residue at P69 (P = 0.0236);Gain of catalytic residue at P69 (P = 0.0236);Gain of catalytic residue at P69 (P = 0.0236);Gain of catalytic residue at P69 (P = 0.0236);
MVP		0.048
MPC		0.097
ClinPred		0.027	T
GERP RS		2.2
Varity_R		0.021
gMVP		0.051

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: chr5-36269555;