chr5-178144043-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_022762.5(RMND5B):​c.629C>T​(p.Ala210Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000112 in 1,614,118 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000011 ( 0 hom. )

Consequence

RMND5B
NM_022762.5 missense

Scores

19

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.18
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.03869441).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
RMND5BNM_022762.5 linkuse as main transcriptc.629C>T p.Ala210Val missense_variant 7/11 ENST00000313386.9 NP_073599.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
RMND5BENST00000313386.9 linkuse as main transcriptc.629C>T p.Ala210Val missense_variant 7/111 NM_022762.5 ENSP00000320623 P1Q96G75-1

Frequencies

GnomAD3 genomes
AF:
0.0000131
AC:
2
AN:
152264
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000384
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000518
AC:
13
AN:
251186
Hom.:
0
AF XY:
0.0000442
AC XY:
6
AN XY:
135832
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000490
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000264
Gnomad OTH exome
AF:
0.000163
GnomAD4 exome
AF:
0.0000109
AC:
16
AN:
1461854
Hom.:
0
Cov.:
32
AF XY:
0.00000963
AC XY:
7
AN XY:
727226
show subpopulations
Gnomad4 AFR exome
AF:
0.0000597
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000151
Gnomad4 SAS exome
AF:
0.0000232
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000450
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
AF:
0.0000131
AC:
2
AN:
152264
Hom.:
0
Cov.:
33
AF XY:
0.00
AC XY:
0
AN XY:
74390
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000384
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000113
Hom.:
0
Bravo
AF:
0.0000264
ExAC
AF:
0.0000247
AC:
3
EpiCase
AF:
0.0000545
EpiControl
AF:
0.00

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 submitterclinical testingAmbry GeneticsApr 09, 2024The c.629C>T (p.A210V) alteration is located in exon 7 (coding exon 5) of the RMND5B gene. This alteration results from a C to T substitution at nucleotide position 629, causing the alanine (A) at amino acid position 210 to be replaced by a valine (V). 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
0.093
BayesDel_addAF
Benign
-0.46
T
BayesDel_noAF
Benign
-0.56
CADD
Benign
16
DANN
Benign
0.95
DEOGEN2
Benign
0.042
T;T;T
Eigen
Benign
-0.77
Eigen_PC
Benign
-0.64
FATHMM_MKL
Benign
0.52
D
LIST_S2
Benign
0.37
.;T;T
M_CAP
Benign
0.0072
T
MetaRNN
Benign
0.039
T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
0.95
L;L;.
MutationTaster
Benign
1.0
N;N;N
PrimateAI
Benign
0.43
T
PROVEAN
Benign
-1.4
N;N;N
REVEL
Benign
0.029
Sift
Benign
0.26
T;T;T
Sift4G
Benign
0.28
T;T;T
Polyphen
0.0020
B;B;B
Vest4
0.14
MutPred
0.32
Gain of helix (P = 0.0325);Gain of helix (P = 0.0325);.;
MVP
0.12
MPC
0.20
ClinPred
0.031
T
GERP RS
3.1
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.034
gMVP
0.15

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.

Other links and lift over

dbSNP: rs774372243; hg19: chr5-177571044; COSMIC: COSV100523171; COSMIC: COSV100523171; API