5-178146140-G-T

Variant names:

• chr5-178146140-G-T
• rs141123042
• NM_022762.5:c.721G>T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_022762.5(RMND5B):​c.721G>T​(p.Val241Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,816 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: RMND5B NM_022762.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 8.19

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.40469196).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RMND5B	NM_022762.5	c.721G>T	p.Val241Leu	missense_variant	Exon 8 of 11	ENST00000313386.9	NP_073599.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RMND5B	ENST00000313386.9	c.721G>T	p.Val241Leu	missense_variant	Exon 8 of 11	1	NM_022762.5	ENSP00000320623.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461816 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727202

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.31
BayesDel_addAF	Pathogenic	0.31	D
BayesDel_noAF	Pathogenic	0.21
CADD	Benign	21
DANN	Benign	0.93
DEOGEN2	Benign	0.027	T;T;T
Eigen	Benign	-0.26
Eigen_PC	Benign	0.037
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Uncertain	0.96	.;D;D
M_CAP	Benign	0.0034	T
MetaRNN	Benign	0.40	T;T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	-0.10	N;N;.
PrimateAI	Uncertain	0.67	T
PROVEAN	Benign	0.26	N;N;N
REVEL	Benign	0.26
Sift	Benign	0.84	T;T;T
Sift4G	Benign	1.0	T;T;T
Polyphen		0.0040	B;B;B
Vest4		0.89
MutPred		0.43		Gain of helix (P = 0.0425);Gain of helix (P = 0.0425);.;
MVP		0.27
MPC		0.20
ClinPred		0.86	D
GERP RS		5.7
Varity_R		0.23
gMVP		0.52

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

Other links and lift over

dbSNP: rs141123042; hg19: chr5-177573141;