14-31561433-C-A

Variant names:

• chr14-31561433-C-A
• rs201073307
• NM_025152.3:c.-7C>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_025152.3(NUBPL):​c.-7C>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000804 in 1,244,476 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 33)
  • Exomes 𝑓: 8.0e-7 (0 hom.)
• Consequence: NUBPL NM_025152.3 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.959
• 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-DT (HGNC:55483): (NUBPL divergent transcript)

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).

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.-7C>A		5_prime_UTR	Exon 1 of 11	NP_079428.2	X5D2R5
	NUBPL	NR_120408.2		n.30C>A		non_coding_transcript_exon	Exon 1 of 10

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NUBPL	ENST00000281081.12	TSL:1 MANE Select	c.-7C>A		5_prime_UTR	Exon 1 of 11	ENSP00000281081.7	Q8TB37-1
	NUBPL	ENST00000858673.1		c.-7C>A		5_prime_UTR	Exon 1 of 12	ENSP00000528732.1
	NUBPL	ENST00000858677.1		c.-7C>A		5_prime_UTR	Exon 1 of 11	ENSP00000528736.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 8.04e-7 AC: 1 AN: 1244476 Hom.: 0 Cov.: 29 AF XY: 0.00000165 AC XY: 1 AN XY: 606872

African (AFR) AF: 0.00 AC: 0 AN: 25954

American (AMR) AF: 0.00 AC: 0 AN: 21372

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18266

East Asian (EAS) AF: 0.00 AC: 0 AN: 30928

South Asian (SAS) AF: 0.00 AC: 0 AN: 50058

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 46422

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4948

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 996576

Other (OTH) AF: 0.0000200 AC: 1 AN: 49952

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	7.0
DANN	Benign	0.54
PhyloP100		-0.96
PromoterAI		-0.11	Neutral

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs201073307; hg19: chr14-32030639;