14-31562039-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_025152.3(NUBPL):c.109-29C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0469 in 1,549,298 control chromosomes in the GnomAD database, including 2,033 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.035 (124 hom., cov: 32)
  • Exomes 𝑓: 0.048 (1909 hom.)
• Consequence: NUBPL NM_025152.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.444

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 14-31562039-C-T is Benign according to our data. Variant chr14-31562039-C-T is described in ClinVar as [Benign]. Clinvar id is 1232898.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0519 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NUBPL	NM_025152.3	c.109-29C>T		intron_variant		ENST00000281081.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NUBPL	ENST00000281081.12	c.109-29C>T		intron_variant		1	NM_025152.3	P1

Frequencies

GnomAD3 genomes AF: 0.0347 AC: 5282 AN: 152068 Hom.: 124 Cov.: 32

Gnomad AFR AF: 0.00988

Gnomad AMI AF: 0.0482

Gnomad AMR AF: 0.0408

Gnomad ASJ AF: 0.0648

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0104

Gnomad FIN AF: 0.0188

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.0533

Gnomad OTH AF: 0.0407

GnomAD3 exomes AF: 0.0356 AC: 5549 AN: 155840 Hom.: 156 AF XY: 0.0354 AC XY: 2939 AN XY: 82950

Gnomad AFR exome AF: 0.00902

Gnomad AMR exome AF: 0.0279

Gnomad ASJ exome AF: 0.0694

Gnomad EAS exome AF: 0.000185

Gnomad SAS exome AF: 0.0137

Gnomad FIN exome AF: 0.0209

Gnomad NFE exome AF: 0.0552

Gnomad OTH exome AF: 0.0443

GnomAD4 exome AF: 0.0483 AC: 67412 AN: 1397112 Hom.: 1909 Cov.: 30 AF XY: 0.0475 AC XY: 32760 AN XY: 689386

Gnomad4 AFR exome AF: 0.00972

Gnomad4 AMR exome AF: 0.0290

Gnomad4 ASJ exome AF: 0.0673

Gnomad4 EAS exome AF: 0.000140

Gnomad4 SAS exome AF: 0.0131

Gnomad4 FIN exome AF: 0.0224

Gnomad4 NFE exome AF: 0.0550

Gnomad4 OTH exome AF: 0.0430

GnomAD4 genome AF: 0.0347 AC: 5281 AN: 152186 Hom.: 124 Cov.: 32 AF XY: 0.0325 AC XY: 2414 AN XY: 74380

Gnomad4 AFR AF: 0.00985

Gnomad4 AMR AF: 0.0407

Gnomad4 ASJ AF: 0.0648

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.0104

Gnomad4 FIN AF: 0.0188

Gnomad4 NFE AF: 0.0533

Gnomad4 OTH AF: 0.0402

Alfa AF: 0.0483 Hom.: 69

Bravo AF: 0.0356

Asia WGS AF: 0.00722 AC: 25 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 07, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
Cadd	Benign	3.4
Dann	Benign	0.70

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: rs77709919; hg19: chr14-32031245;