rs886050447

Variant names:

• chr14-31561485-C-A
• rs886050447
• NM_025152.3:c.46C>A

Your query was ambiguous. Multiple possible variants found:

• chr14-31561485-C-A
• chr14-31561485-C-G
• chr14-31561485-C-T

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_025152.3(NUBPL):​c.46C>A​(p.Arg16Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000798 in 1,252,996 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 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.184
• 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 -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.59).
• BP7: Synonymous conserved (PhyloP=-0.184 with no splicing effect.

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.46C>A	p.Arg16Arg	synonymous	Exon 1 of 11	NP_079428.2	X5D2R5
	NUBPL	NR_120408.2		n.82C>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.46C>A	p.Arg16Arg	synonymous	Exon 1 of 11	ENSP00000281081.7	Q8TB37-1
	NUBPL	ENST00000858673.1		c.46C>A	p.Arg16Arg	synonymous	Exon 1 of 12	ENSP00000528732.1
	NUBPL	ENST00000858677.1		c.46C>A	p.Arg16Arg	synonymous	Exon 1 of 11	ENSP00000528736.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.98e-7 AC: 1 AN: 1252996 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 612500

African (AFR) AF: 0.00 AC: 0 AN: 26038

American (AMR) AF: 0.00 AC: 0 AN: 22076

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18328

East Asian (EAS) AF: 0.00 AC: 0 AN: 31300

South Asian (SAS) AF: 0.00 AC: 0 AN: 50878

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 46468

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4956

European-Non Finnish (NFE) AF: 9.97e-7 AC: 1 AN: 1002818

Other (OTH) AF: 0.00 AC: 0 AN: 50134

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
CADD	Benign	8.4
DANN	Benign	0.58
PhyloP100		-0.18
PromoterAI		-0.17	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs886050447; hg19: chr14-32030691;