Variant 2-86741016-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_022780.4(RMND5A):c.232G>A(p.Asp78Asn) variant causes a missense change. The variant allele was found at a frequency of 0.000223 in 152,282 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: 𝑓 0.00022 ( 0 hom., cov: 26)

Exomes 𝑓: 0.000059 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

RMND5A
NM_022780.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.70

Variant links:

Genes affected

RMND5A (HGNC:25850): (required for meiotic nuclear division 5 homolog A) 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 and protein polyubiquitination. Located in cytoplasm and nucleoplasm. Part of ubiquitin ligase complex. [provided by Alliance of Genome Resources, Apr 2022]

RMND5A links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.13950142).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RMND5A	NM_022780.4 link	c.232G>A	p.Asp78Asn	missense_variant	2/9	ENST00000283632.5	NP_073617.1	Q9H871-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RMND5A	ENST00000283632.5 link	c.232G>A	p.Asp78Asn	missense_variant	2/9	1	NM_022780.4	ENSP00000283632.4		Q9H871-1

Frequencies

GnomAD3 genomes

AF:

0.000223

AC:

AN:

152164

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00170

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000769

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.000478

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000588

AC:

AN:

1461406

Hom.:

Cov.:

AF XY:

0.0000509

AC XY:

AN XY:

727012

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.000269

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000176

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000495

Gnomad4 OTH exome

AF:

0.000182

GnomAD4 genome

AF:

0.000223

AC:

AN:

152282

Hom.:

Cov.:

AF XY:

0.000242

AC XY:

AN XY:

74446

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00170

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000771

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000144

Hom.:

ExAC

AF:

0.000107

AC:

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

Nov 22, 2023

The c.232G>A (p.D78N) alteration is located in exon 2 (coding exon 2) of the RMND5A gene. This alteration results from a G to A substitution at nucleotide position 232, causing the aspartic acid (D) at amino acid position 78 to be replaced by an asparagine (N). 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

-0.16

BayesDel_noAF

Benign

-0.47

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.028

Eigen

Benign

0.11

Eigen_PC

Uncertain

0.28

FATHMM_MKL

Uncertain

0.94

LIST_S2

Uncertain

0.97

M_CAP

Benign

0.0061

MetaRNN

Benign

0.14

MetaSVM

Benign

-0.87

MutationAssessor

Benign

1.8

PrimateAI

Pathogenic

0.89

PROVEAN

Benign

-1.8

REVEL

Benign

0.054

Sift

Benign

0.050

Sift4G

Benign

0.17

Polyphen

0.23

Vest4

0.53

MutPred

0.34

Loss of stability (P = 0.0258);

MVP

0.27

MPC

1.0

ClinPred

0.086

GERP RS

5.7

Varity_R

0.20

gMVP

0.47

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