Variant chr5-178142870-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_022762.5(RMND5B):c.304T>C(p.Cys102Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,892 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

RMND5B
NM_022762.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.11

Variant links:

Genes affected

RMND5B (HGNC:26181): (required for meiotic nuclear division 5 homolog B) Predicted to enable metal ion binding activity and ubiquitin protein ligase activity. Predicted to contribute to ubiquitin-protein transferase activity. Predicted to be involved in proteasome-mediated ubiquitin-dependent protein catabolic process. Located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

RMND5B links:

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ACMG classification

Classification made for transcript

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=0.21148452).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RMND5B	NM_022762.5 linkuse as main transcript	c.304T>C	p.Cys102Arg	missense_variant	5/11	ENST00000313386.9	NP_073599.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RMND5B	ENST00000313386.9 linkuse as main transcript	c.304T>C	p.Cys102Arg	missense_variant	5/11	1	NM_022762.5	ENSP00000320623	P1	Q96G75-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000795

AC:

AN:

251480

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135912

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461892

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727246

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

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.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 03, 2023

The c.304T>C (p.C102R) alteration is located in exon 5 (coding exon 3) of the RMND5B gene. This alteration results from a T to C substitution at nucleotide position 304, causing the cysteine (C) at amino acid position 102 to be replaced by an arginine (R). 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

0.24

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.25

CADD

Uncertain

DANN

Benign

0.84

DEOGEN2

Benign

0.081

T;T;.;T;T

Eigen

Benign

-0.43

Eigen_PC

Benign

-0.29

FATHMM_MKL

Uncertain

0.79

LIST_S2

Uncertain

0.91

.;D;D;D;D

M_CAP

Benign

0.0082

MetaRNN

Benign

0.21

T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.69

N;N;.;.;.

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.71

PROVEAN

Benign

-2.2

N;N;N;N;N

REVEL

Benign

0.23

Sift

Benign

0.052

T;T;D;D;T

Sift4G

Benign

0.20

T;T;T;T;T

Polyphen

0.017

B;B;.;.;B

Vest4

0.71

MutPred

0.40

Gain of MoRF binding (P = 0.0081);Gain of MoRF binding (P = 0.0081);Gain of MoRF binding (P = 0.0081);Gain of MoRF binding (P = 0.0081);.;

MVP

0.52

MPC

0.34

ClinPred

0.16

GERP RS

3.5

Varity_R

0.46

gMVP

0.56

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. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over