Genetic Variant RANBP10:p.Ser579Phe (chr16-67726555-G-A) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

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

The NM_020850.3(RANBP10):c.1736C>T(p.Ser579Phe) variant causes a missense change. The variant allele was found at a frequency of 0.00000285 in 1,402,346 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000029 ( 0 hom. )

Consequence

RANBP10
NM_020850.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.81

Variant links:

Genes affected

RANBP10 (HGNC:29285): (RAN binding protein 10) RAN is a small GTPase involved in the assembly of microtubules to form mitotic spindles. The protein encoded by this gene is a cytoplasmic guanine nucleotide exchange factor (GEF) that binds beta-tubulin and has GEF activity toward RAN. The encoded protein plays a role in the formation of noncentrosomal microtubules. In addition, this protein may be involved in the regulation of D(1) receptor signaling by protein kinase C delta and protein kinase C gamma. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Feb 2016]

RANBP10 links:

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ACMG classification

Classification was made for transcript

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
RANBP10	NM_020850.3 link	c.1736C>T	p.Ser579Phe	missense_variant	Exon 14 of 14	ENST00000317506.8	NP_065901.1	Q6VN20-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RANBP10	ENST00000317506.8 link	c.1736C>T	p.Ser579Phe	missense_variant	Exon 14 of 14	1	NM_020850.3	ENSP00000316589.3		Q6VN20-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000631

AC:

AN:

158356

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000162

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000285

AC:

AN:

1402346

Hom.:

Cov.:

AF XY:

0.00000289

AC XY:

AN XY:

692166

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31854

American (AMR)

AF:

0.00

AC:

AN:

35944

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25104

East Asian (EAS)

AF:

0.00

AC:

AN:

36108

South Asian (SAS)

AF:

0.00

AC:

AN:

79526

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49304

Middle Eastern (MID)

AF:

0.000176

AC:

AN:

5696

European-Non Finnish (NFE)

AF:

0.00000278

AC:

AN:

1080660

Other (OTH)

AF:

0.00

AC:

AN:

58150

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.550

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Feb 23, 2023

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.1736C>T (p.S579F) alteration is located in exon 14 (coding exon 14) of the RANBP10 gene. This alteration results from a C to T substitution at nucleotide position 1736, causing the serine (S) at amino acid position 579 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

Uncertain

0.45

BayesDel_addAF

Pathogenic

0.46

BayesDel_noAF

Pathogenic

0.42

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.31

T;.;.;.

Eigen

Pathogenic

0.83

Eigen_PC

Pathogenic

0.83

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.90

D;D;D;D

M_CAP

Benign

0.022

MetaRNN

Uncertain

0.51

D;D;D;D

MetaSVM

Uncertain

-0.28

MutationAssessor

Pathogenic

3.0

M;.;.;.

PhyloP100

6.8

PrimateAI

Pathogenic

0.86

PROVEAN

Pathogenic

-4.6

D;.;D;.

REVEL

Uncertain

0.51

Sift

Benign

0.13

T;.;D;.

Sift4G

Benign

0.10

T;T;D;D

Polyphen

0.92

P;.;.;.

Vest4

0.54

MutPred

0.73

Loss of disorder (P = 0.0015);Loss of disorder (P = 0.0015);.;.;

MVP

0.41

MPC

1.1

ClinPred

0.97

GERP RS

5.7

Varity_R

0.46

gMVP

0.73

Mutation Taster

=43/57

disease causing

(source)

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

LitVar

Below is the list of publications found by LitVar for variant 16:67726555 G>A . It may be empty.

16-67726555-G-A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over