14-31561189-T-G

Position:

• chr14-31561189-T-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The ENST00000548096.1(NUBPL-DT):​n.146A>C variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00845 in 360,238 control chromosomes in the GnomAD database, including 90 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.017 (80 hom., cov: 33)
  • Exomes 𝑓: 0.0022 (10 hom.)
• Consequence: NUBPL-DT ENST00000548096.1 non_coding_transcript_exon
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.760

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 14-31561189-T-G is Benign according to our data. Variant chr14-31561189-T-G is described in ClinVar as [Benign]. Clinvar id is 1234109.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) 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.143A>C		non_coding_transcript_exon_variant	1/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NUBPL-DT	ENST00000548096.1	n.146A>C		non_coding_transcript_exon_variant	1/2	3
NUBPL	ENST00000550005.1	c.34-879T>G		intron_variant		4		ENSP00000446511

Frequencies

GnomAD3 genomes AF: 0.0170 AC: 2583 AN: 152174 Hom.: 80 Cov.: 33

Gnomad AFR AF: 0.0587

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00759

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000415

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000162

Gnomad OTH AF: 0.0105

GnomAD4 exome AF: 0.00220 AC: 457 AN: 207946 Hom.: 10 Cov.: 0 AF XY: 0.00181 AC XY: 191 AN XY: 105356

Gnomad4 AFR exome AF: 0.0529

Gnomad4 AMR exome AF: 0.00453

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: 0.0000966

Gnomad4 OTH exome AF: 0.00527

GnomAD4 genome AF: 0.0170 AC: 2586 AN: 152292 Hom.: 80 Cov.: 33 AF XY: 0.0170 AC XY: 1264 AN XY: 74478

Gnomad4 AFR AF: 0.0586

Gnomad4 AMR AF: 0.00758

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000162

Gnomad4 OTH AF: 0.0104

Alfa AF: 0.00903 Hom.: 5

Bravo AF: 0.0190

Asia WGS AF: 0.00260 AC: 9 AN: 3478

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

Aug 03, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	8.4
DANN	Benign	0.52

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs74040870; hg19: chr14-32030395;