Genetic Variant NUBPL:p.Leu25Pro (chr14-31561513-T-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_025152.3(NUBPL):c.74T>C(p.Leu25Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

NUBPL
NM_025152.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.206

Publications

0 publications found

Variant links:

Genes affected

NUBPL (HGNC:20278): (NUBP iron-sulfur cluster assembly factor, mitochondrial) This gene encodes a member of the Mrp/NBP35 ATP-binding proteins family. The encoded protein is required for the assembly of the respiratory chain NADH dehydrogenase (complex I), an oligomeric enzymatic complex located in the inner mitochondrial membrane. Mutations in this gene cause mitochondrial complex I deficiency. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2014]

NUBPL links:

NUBPL-DT (HGNC:55483): (NUBPL divergent transcript)

NUBPL-DT links:

Genome browser will be placed here

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=0.08075285).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_025152.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NUBPL	NM_025152.3	MANE Select	c.74T>C	p.Leu25Pro	missense	Exon 1 of 11	NP_079428.2	X5D2R5
	NUBPL	NR_120408.2		n.110T>C		non_coding_transcript_exon	Exon 1 of 10

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NUBPL	ENST00000281081.12	TSL:1 MANE Select	c.74T>C	p.Leu25Pro	missense	Exon 1 of 11	ENSP00000281081.7	Q8TB37-1
NUBPL	ENST00000858673.1		c.74T>C	p.Leu25Pro	missense	Exon 1 of 12	ENSP00000528732.1
NUBPL	ENST00000858677.1		c.74T>C	p.Leu25Pro	missense	Exon 1 of 11	ENSP00000528736.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1231956

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

599890

African (AFR)

AF:

0.00

AC:

AN:

25460

American (AMR)

AF:

0.00

AC:

AN:

19296

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

16920

East Asian (EAS)

AF:

0.00

AC:

AN:

31202

South Asian (SAS)

AF:

0.00

AC:

AN:

46400

European-Finnish (FIN)

AF:

0.00

AC:

AN:

45084

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4822

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

993526

Other (OTH)

AF:

0.00

AC:

AN:

49246

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.054

BayesDel_addAF

Benign

-0.080

BayesDel_noAF

Benign

-0.35

CADD

Benign

(source)

DANN

Benign

0.75

DEOGEN2

Benign

0.0026

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.0079

LIST_S2

Benign

0.50

M_CAP

Benign

0.0062

MetaRNN

Benign

0.081

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.81

PhyloP100

-0.21

PrimateAI

Benign

0.39

PROVEAN

Benign

-0.47

REVEL

Benign

0.025

Sift

Benign

0.21

Sift4G

Benign

0.092

Polyphen

0.0010

Vest4

0.25

MutPred

0.44

Gain of relative solvent accessibility (P = 0.0098)

MVP

0.31

MPC

0.19

ClinPred

0.092

GERP RS

0.82

PromoterAI

-0.096

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.13

gMVP

0.61

Mutation Taster

=93/7

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over