14-31561516-G-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2

The NM_025152.3(NUBPL):c.77G>T(p.Gly26Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000792 in 1,383,064 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.0042 ( 5 hom., cov: 32)

Exomes 𝑓: 0.00037 ( 3 hom. )

Consequence

NUBPL
NM_025152.3 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:6

Conservation

PhyloP100: 0.567

Publications

4 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: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0043064356).

BP6

Variant 14-31561516-G-T is Benign according to our data. Variant chr14-31561516-G-T is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 282798.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00423 (644/152372) while in subpopulation AFR AF = 0.0144 (597/41584). AF 95% confidence interval is 0.0134. There are 5 homozygotes in GnomAd4. There are 321 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 5 AR gene

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.77G>T	p.Gly26Val	missense	Exon 1 of 11	NP_079428.2	X5D2R5
	NUBPL	NR_120408.2		n.113G>T		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.77G>T	p.Gly26Val	missense	Exon 1 of 11	ENSP00000281081.7	Q8TB37-1
NUBPL	ENST00000858673.1		c.77G>T	p.Gly26Val	missense	Exon 1 of 12	ENSP00000528732.1
NUBPL	ENST00000858677.1		c.77G>T	p.Gly26Val	missense	Exon 1 of 11	ENSP00000528736.1

Frequencies

GnomAD3 genomes

AF:

0.00423

AC:

644

AN:

152254

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0144

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00255

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00334

GnomAD2 exomes

AF:

0.00112

AC:

131

AN:

116580

AF XY:

0.000829

show subpopulations

Gnomad AFR exome

AF:

0.0141

Gnomad AMR exome

AF:

0.000464

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00246

GnomAD4 exome

AF:

0.000367

AC:

452

AN:

1230692

Hom.:

Cov.:

AF XY:

0.000317

AC XY:

190

AN XY:

598756

show subpopulations

African (AFR)

AF:

0.0150

AC:

382

AN:

25398

American (AMR)

AF:

0.000887

AC:

AN:

19176

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

16818

East Asian (EAS)

AF:

0.00

AC:

AN:

31172

South Asian (SAS)

AF:

0.00

AC:

AN:

46372

European-Finnish (FIN)

AF:

0.00

AC:

AN:

44954

Middle Eastern (MID)

AF:

0.000207

AC:

AN:

4824

European-Non Finnish (NFE)

AF:

0.00000403

AC:

AN:

992750

Other (OTH)

AF:

0.000975

AC:

AN:

49228

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

115

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00423

AC:

644

AN:

152372

Hom.:

Cov.:

AF XY:

0.00431

AC XY:

321

AN XY:

74520

show subpopulations

African (AFR)

AF:

0.0144

AC:

597

AN:

41584

American (AMR)

AF:

0.00255

AC:

AN:

15310

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68038

Other (OTH)

AF:

0.00331

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

102

136

170

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00174

Hom.:

Bravo

AF:

0.00478

ESP6500AA

AF:

0.0123

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00107

AC:

128

Asia WGS

AF:

0.00115

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Conflicting classifications of pathogenicity

Revision:criteria provided, conflicting classifications

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

not specified (2)

Mitochondrial complex I deficiency, nuclear type 1 (1)

NUBPL-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.085

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.33

CADD

Benign

(source)

DANN

Benign

0.76

DEOGEN2

Benign

0.0061

Eigen

Benign

-0.84

Eigen_PC

Benign

-0.81

FATHMM_MKL

Benign

0.018

LIST_S2

Benign

0.66

MetaRNN

Benign

0.0043

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.4

PhyloP100

0.57

PrimateAI

Benign

0.35

PROVEAN

Benign

0.11

REVEL

Benign

0.037

Sift

Benign

0.12

Sift4G

Benign

0.22

Polyphen

0.041

Vest4

0.40

MVP

0.54

MPC

0.15

ClinPred

0.017

GERP RS

3.5

PromoterAI

0.034

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.076

gMVP

0.38

Mutation Taster

=96/4

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over