14-31787858-AAT-TCC

Variant names:

• chr14-31787858-AAT-TCC
• NM_025152.3:c.592_594delAATinsTCC
• NUBPL p.Asn198Ser

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 1P and 0B. PP3

The NM_025152.3(NUBPL):​c.592_594delAATinsTCC​(p.Asn198Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. N198T) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: NUBPL NM_025152.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.97
• 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: Uncertain_significance. The variant received 1 ACMG points.

• PP3: No computational evidence supports a deleterious effect, but strongly conserved according to phyloP

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.592_594delAATinsTCC	p.Asn198Ser	missense	N/A	NP_079428.2	X5D2R5
	NUBPL	NM_001201573.2		c.304_306delAATinsTCC	p.Asn102Ser	missense	N/A	NP_001188502.1	B4DWB0
	NUBPL	NM_001201574.2		c.43_45delAATinsTCC	p.Asn15Ser	missense	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.592_594delAATinsTCC	p.Asn198Ser	missense	N/A	ENSP00000281081.7	Q8TB37-1
	NUBPL	ENST00000858673.1		c.592_594delAATinsTCC	p.Asn198Ser	missense	N/A	ENSP00000528732.1
	NUBPL	ENST00000858677.1		c.586_588delAATinsTCC	p.Asn196Ser	missense	N/A	ENSP00000528736.1

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		8.0

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr14-32257064;