Genetic Variant RANBP3L:p.Ser162Cys (chr5-36262038-G-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_145000.5(RANBP3L):c.485C>G(p.Ser162Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000291 in 1,375,910 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S162F) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000029 ( 0 hom. )

Consequence

RANBP3L
NM_145000.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.12

Publications

1 publications found

Variant links:

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]

RANBP3L links:

LOC124900962 (HGNC:):

LOC124900962 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.16822463).

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RANBP3L	NM_145000.5	MANE Select	c.485C>G	p.Ser162Cys	missense	Exon 7 of 14	NP_659437.3
RANBP3L	NM_001323273.2		c.485C>G	p.Ser162Cys	missense	Exon 7 of 14	NP_001310202.1
RANBP3L	NM_001161429.3		c.560C>G	p.Ser187Cys	missense	Exon 8 of 15	NP_001154901.1	Q86VV4-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RANBP3L	ENST00000296604.8	TSL:1 MANE Select	c.485C>G	p.Ser162Cys	missense	Exon 7 of 14	ENSP00000296604.3	Q86VV4-1
RANBP3L	ENST00000502994.5	TSL:2	c.560C>G	p.Ser187Cys	missense	Exon 8 of 15	ENSP00000421853.1	Q86VV4-3
RANBP3L	ENST00000900326.1		c.485C>G	p.Ser162Cys	missense	Exon 7 of 14	ENSP00000570385.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000291

AC:

AN:

1375910

Hom.:

Cov.:

AF XY:

0.00000435

AC XY:

AN XY:

689336

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31452

American (AMR)

AF:

0.00

AC:

AN:

43690

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25440

East Asian (EAS)

AF:

0.00

AC:

AN:

39042

South Asian (SAS)

AF:

0.00

AC:

AN:

83236

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53152

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5588

European-Non Finnish (NFE)

AF:

0.00000386

AC:

AN:

1036986

Other (OTH)

AF:

0.00

AC:

AN:

57324

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.512

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.093

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.49

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.016

Eigen

Uncertain

0.21

Eigen_PC

Benign

0.13

FATHMM_MKL

Uncertain

0.79

LIST_S2

Benign

0.63

M_CAP

Benign

0.010

MetaRNN

Benign

0.17

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.4

PhyloP100

2.1

PrimateAI

Benign

0.29

PROVEAN

Benign

-2.2

REVEL

Benign

0.064

Sift

Uncertain

0.013

Sift4G

Uncertain

0.035

Polyphen

0.99

Vest4

0.25

MutPred

0.30

Loss of disorder (P = 0.0311)

MVP

0.24

MPC

0.41

ClinPred

0.92

GERP RS

3.2

Varity_R

0.12

gMVP

0.33

Mutation Taster

=89/11

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.16

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over