rs7142881

Variant names:

• chr14-31624342-G-A
• rs7142881
• NM_025152.3:c.382+24963G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_025152.3(NUBPL):​c.382+24963G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.454 in 151,916 control chromosomes in the GnomAD database, including 17,079 homozygotes. 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: 𝑓 0.45 (17079 hom., cov: 31)
• Consequence: NUBPL NM_025152.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0120
• Publications: 20 publications found

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 Gene-Disease associations (from GenCC):

• mitochondrial complex I deficiency, nuclear type 21

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)
• mitochondrial disease

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• Leigh syndrome

  Inheritance: AR Classification: MODERATE Submitted by: ClinGen
• mitochondrial complex I deficiency

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.59).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.583 is higher than 0.05.

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.382+24963G>A		intron	N/A	NP_079428.2	X5D2R5
	NUBPL	NM_001201573.2		c.94+24963G>A		intron	N/A	NP_001188502.1	B4DWB0
	NUBPL	NR_120408.2		n.418+24963G>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NUBPL	ENST00000281081.12	TSL:1 MANE Select	c.382+24963G>A		intron	N/A	ENSP00000281081.7	Q8TB37-1
	NUBPL	ENST00000858673.1		c.382+24963G>A		intron	N/A	ENSP00000528732.1
	NUBPL	ENST00000858677.1		c.376+24963G>A		intron	N/A	ENSP00000528736.1

Frequencies

GnomAD3 genomes AF: 0.454 AC: 68879 AN: 151798 Hom.: 17066 Cov.: 31

Gnomad AFR AF: 0.240

Gnomad AMI AF: 0.523

Gnomad AMR AF: 0.530

Gnomad ASJ AF: 0.529

Gnomad EAS AF: 0.602

Gnomad SAS AF: 0.520

Gnomad FIN AF: 0.505

Gnomad MID AF: 0.462

Gnomad NFE AF: 0.537

Gnomad OTH AF: 0.483

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.454 AC: 68909 AN: 151916 Hom.: 17079 Cov.: 31 AF XY: 0.456 AC XY: 33831 AN XY: 74254

African (AFR) AF: 0.240 AC: 9938 AN: 41424

American (AMR) AF: 0.530 AC: 8088 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.529 AC: 1836 AN: 3472

East Asian (EAS) AF: 0.601 AC: 3099 AN: 5158

South Asian (SAS) AF: 0.521 AC: 2503 AN: 4806

European-Finnish (FIN) AF: 0.505 AC: 5327 AN: 10548

Middle Eastern (MID) AF: 0.459 AC: 135 AN: 294

European-Non Finnish (NFE) AF: 0.537 AC: 36481 AN: 67936

Other (OTH) AF: 0.487 AC: 1029 AN: 2112

Alfa AF: 0.517 Hom.: 98002

Bravo AF: 0.447

Asia WGS AF: 0.558 AC: 1940 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
CADD	Benign	4.5
DANN	Benign	0.72
PhyloP100		0.012
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs7142881; hg19: chr14-32093548;