14-31561083-GT-G

Position:

• chr14-31561083-GT-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The ENST00000548096.1(NUBPL-DT):​n.224+27del variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0428 in 186,078 control chromosomes in the GnomAD database, including 223 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.041 (182 hom., cov: 32)
  • Exomes 𝑓: 0.049 (41 hom.)
• Consequence: NUBPL-DT ENST00000548096.1 intron, non_coding_transcript
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.511

Genes affected

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

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 -10 ACMG points.

• BP6: Variant 14-31561083-GT-G is Benign according to our data. Variant chr14-31561083-GT-G is described in ClinVar as [Benign]. Clinvar id is 1283520.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0567 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NUBPL-DT	XR_943720.2	n.221+27del		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NUBPL-DT	ENST00000548096.1	n.224+27del		intron_variant, non_coding_transcript_variant		3
NUBPL	ENST00000550005.1	c.34-984del		intron_variant		4		ENSP00000446511

Frequencies

GnomAD3 genomes AF: 0.0415 AC: 6311 AN: 152064 Hom.: 182 Cov.: 32

Gnomad AFR AF: 0.00925

Gnomad AMI AF: 0.0406

Gnomad AMR AF: 0.0274

Gnomad ASJ AF: 0.0570

Gnomad EAS AF: 0.00115

Gnomad SAS AF: 0.0556

Gnomad FIN AF: 0.0876

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.0583

Gnomad OTH AF: 0.0460

GnomAD4 exome AF: 0.0487 AC: 1652 AN: 33896 Hom.: 41 Cov.: 0 AF XY: 0.0504 AC XY: 857 AN XY: 16992

Gnomad4 AFR exome AF: 0.00803

Gnomad4 AMR exome AF: 0.0228

Gnomad4 ASJ exome AF: 0.0537

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0562

Gnomad4 FIN exome AF: 0.0943

Gnomad4 NFE exome AF: 0.0531

Gnomad4 OTH exome AF: 0.0524

GnomAD4 genome AF: 0.0415 AC: 6309 AN: 152182 Hom.: 182 Cov.: 32 AF XY: 0.0441 AC XY: 3282 AN XY: 74410

Gnomad4 AFR AF: 0.00922

Gnomad4 AMR AF: 0.0274

Gnomad4 ASJ AF: 0.0570

Gnomad4 EAS AF: 0.00116

Gnomad4 SAS AF: 0.0560

Gnomad4 FIN AF: 0.0876

Gnomad4 NFE AF: 0.0583

Gnomad4 OTH AF: 0.0450

Alfa AF: 0.0318 Hom.: 23

Bravo AF: 0.0337

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

Jun 29, 2018

- -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs71115020; hg19: chr14-32030289;