19-5925637-G-A

Position:

• chr19-5925637-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_007322.3(RANBP3):​c.914C>T​(p.Ser305Phe) 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.

• Frequency: Genomes: not found (cov: 32)
• Consequence: RANBP3 NM_007322.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.06

Genes affected

RANBP3 (HGNC:9850): (RAN binding protein 3) This gene encodes a protein with a RanBD1 domain that is found in both the nucleus and cytoplasm. This protein plays a role in nuclear export as part of a heteromeric complex. Alternate transcriptional splice variants, encoding different isoforms, have been characterized. [provided by RefSeq, Jul 2008]

RANBP3 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.18003711).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RANBP3	NM_007322.3	c.914C>T	p.Ser305Phe	missense_variant	10/17	ENST00000340578.10	NP_015561.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RANBP3	ENST00000340578.10	c.914C>T	p.Ser305Phe	missense_variant	10/17	1	NM_007322.3	ENSP00000341483.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

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

Nov 14, 2024

The c.914C>T (p.S305F) alteration is located in exon 10 (coding exon 10) of the RANBP3 gene. This alteration results from a C to T substitution at nucleotide position 914, causing the serine (S) at amino acid position 305 to be replaced by a phenylalanine (F). 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	0.23
BayesDel_addAF	Benign	-0.061	T
BayesDel_noAF	Benign	-0.33
CADD	Uncertain	25
DANN	Uncertain	0.98
DEOGEN2	Benign	0.098	.;T;T;.;T;.
Eigen	Benign	-0.17
Eigen_PC	Benign	-0.040
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Uncertain	0.89	D;D;D;D;D;D
M_CAP	Benign	0.020	T
MetaRNN	Benign	0.18	T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.0	.;M;.;.;.;.
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-1.7	N;N;.;N;.;.
REVEL	Benign	0.073
Sift	Benign	0.089	T;T;.;T;.;.
Sift4G	Benign	0.34	T;T;T;T;T;T
Polyphen		0.013	B;B;B;B;.;.
Vest4		0.65
MutPred		0.39		.;Loss of disorder (P = 0.0097);.;.;.;.;
MVP		0.54
MPC		0.57
ClinPred		0.49	T
GERP RS		3.0
Varity_R		0.074
gMVP		0.39

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: chr19-5925648; COSMIC: COSV105004418; COSMIC: COSV105004418;