chr14-31561456-G-T

Variant names:

• chr14-31561456-G-T
• NM_025152.3:c.17G>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_025152.3(NUBPL):​c.17G>T​(p.Arg6Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000158 in 1,266,996 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000016 (0 hom.)
• Consequence: NUBPL NM_025152.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.790

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-DT (HGNC:55483): (NUBPL divergent transcript)

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.14055973).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NUBPL	NM_025152.3	c.17G>T	p.Arg6Leu	missense_variant	Exon 1 of 11	ENST00000281081.12	NP_079428.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NUBPL	ENST00000281081.12	c.17G>T	p.Arg6Leu	missense_variant	Exon 1 of 11	1	NM_025152.3	ENSP00000281081.7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000158 AC: 2 AN: 1266996 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 620634

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000198

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Uncertain	0.062	T
BayesDel_noAF	Benign	-0.15
CADD	Benign	17
DANN	Benign	0.92
DEOGEN2	Benign	0.034	T;T
Eigen	Benign	-0.76
Eigen_PC	Benign	-0.82
FATHMM_MKL	Benign	0.032	N
LIST_S2	Benign	0.82	T;T
M_CAP	Benign	0.027	D
MetaRNN	Benign	0.14	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.9	.;L
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-1.2	N;N
REVEL	Benign	0.11
Sift	Pathogenic	0.0	D;D
Sift4G	Pathogenic	0.0	D;T
Polyphen		0.36	.;B
Vest4		0.59
MutPred		0.51		Loss of MoRF binding (P = 0.0015);Loss of MoRF binding (P = 0.0015);
MVP		0.53
MPC		0.28
ClinPred		0.84	D
GERP RS		0.44
Varity_R		0.12
gMVP		0.60

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr14-32030662; COSMIC: COSV55273417; COSMIC: COSV55273417;