rs17098211

Variant names:

• chr14-31845989-A-G
• rs17098211
• NM_025152.3:c.694-482A>G

Variant summary

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

The NM_025152.3(NUBPL):​c.694-482A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.156 in 179,470 control chromosomes in the GnomAD database, including 7,438 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 0.18 (7396 hom., cov: 32)
  • Exomes 𝑓: 0.018 (42 hom.)
• Consequence: NUBPL NM_025152.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00400
• Publications: 0 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=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.581 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.694-482A>G		intron	N/A	NP_079428.2	X5D2R5
	NUBPL	NM_001201573.2		c.406-482A>G		intron	N/A	NP_001188502.1	B4DWB0
	NUBPL	NM_001201574.2		c.145-482A>G		intron	N/A	NP_001188503.1	B3KSK2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NUBPL	ENST00000281081.12	TSL:1 MANE Select	c.694-482A>G		intron	N/A	ENSP00000281081.7	Q8TB37-1
	NUBPL	ENST00000858673.1		c.814-482A>G		intron	N/A	ENSP00000528732.1
	NUBPL	ENST00000858677.1		c.688-482A>G		intron	N/A	ENSP00000528736.1

Frequencies

GnomAD3 genomes AF: 0.180 AC: 27381 AN: 152096 Hom.: 7366 Cov.: 32

Gnomad AFR AF: 0.587

Gnomad AMI AF: 0.138

Gnomad AMR AF: 0.0887

Gnomad ASJ AF: 0.0655

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0120

Gnomad FIN AF: 0.00773

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.0129

Gnomad OTH AF: 0.158

GnomAD4 exome AF: 0.0176 AC: 480 AN: 27256 Hom.: 42 Cov.: 0 AF XY: 0.0175 AC XY: 249 AN XY: 14234

African (AFR) AF: 0.504 AC: 136 AN: 270

American (AMR) AF: 0.0470 AC: 123 AN: 2618

Ashkenazi Jewish (ASJ) AF: 0.0619 AC: 28 AN: 452

East Asian (EAS) AF: 0.00 AC: 0 AN: 1472

South Asian (SAS) AF: 0.00973 AC: 29 AN: 2982

European-Finnish (FIN) AF: 0.00425 AC: 4 AN: 942

Middle Eastern (MID) AF: 0.103 AC: 7 AN: 68

European-Non Finnish (NFE) AF: 0.00729 AC: 125 AN: 17158

Other (OTH) AF: 0.0216 AC: 28 AN: 1294

GnomAD4 genome AF: 0.180 AC: 27463 AN: 152214 Hom.: 7396 Cov.: 32 AF XY: 0.174 AC XY: 12986 AN XY: 74444

African (AFR) AF: 0.588 AC: 24366 AN: 41472

American (AMR) AF: 0.0886 AC: 1356 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0655 AC: 227 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.0118 AC: 57 AN: 4830

European-Finnish (FIN) AF: 0.00773 AC: 82 AN: 10614

Middle Eastern (MID) AF: 0.133 AC: 39 AN: 294

European-Non Finnish (NFE) AF: 0.0129 AC: 878 AN: 68024

Other (OTH) AF: 0.157 AC: 332 AN: 2112

Alfa AF: 0.0727 Hom.: 2741

Bravo AF: 0.205

Asia WGS AF: 0.0410 AC: 143 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	3.2
DANN	Benign	0.80
PhyloP100		0.0040
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: rs17098211; hg19: chr14-32315195;