12-94993980-C-T

Variant summary

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

The NM_018838.5(NDUFA12):c.257+190G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.392 in 151,726 control chromosomes in the GnomAD database, including 12,218 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.39 (12218 hom., cov: 31)
• Consequence: NDUFA12 NM_018838.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.05

Genes affected

NDUFA12 (HGNC:23987): (NADH:ubiquinone oxidoreductase subunit A12) This gene encodes a protein which is part of mitochondrial complex 1, part of the oxidative phosphorylation system in mitochondria. Complex 1 transfers electrons to ubiquinone from NADH which establishes a proton gradient for the generation of ATP. Mutations in this gene are associated with Leigh syndrome due to mitochondrial complex 1 deficiency. Pseudogenes of this gene are located on chromosomes 5 and 13. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Apr 2012]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BP6: Variant 12-94993980-C-T is Benign according to our data. Variant chr12-94993980-C-T is described in ClinVar as [Benign]. Clinvar id is 682690.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.561 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NDUFA12	NM_018838.5	c.257+190G>A		intron_variant		ENST00000327772.7
NDUFA12	NM_001258338.2	c.169+8759G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NDUFA12	ENST00000327772.7	c.257+190G>A		intron_variant		1	NM_018838.5	P1

Frequencies

GnomAD3 genomes AF: 0.392 AC: 59379 AN: 151608 Hom.: 12199 Cov.: 31

Gnomad AFR AF: 0.288

Gnomad AMI AF: 0.421

Gnomad AMR AF: 0.508

Gnomad ASJ AF: 0.456

Gnomad EAS AF: 0.578

Gnomad SAS AF: 0.400

Gnomad FIN AF: 0.282

Gnomad MID AF: 0.446

Gnomad NFE AF: 0.426

Gnomad OTH AF: 0.422

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.392 AC: 59422 AN: 151726 Hom.: 12218 Cov.: 31 AF XY: 0.388 AC XY: 28808 AN XY: 74176

Gnomad4 AFR AF: 0.288

Gnomad4 AMR AF: 0.509

Gnomad4 ASJ AF: 0.456

Gnomad4 EAS AF: 0.578

Gnomad4 SAS AF: 0.398

Gnomad4 FIN AF: 0.282

Gnomad4 NFE AF: 0.426

Gnomad4 OTH AF: 0.428

Alfa AF: 0.287 Hom.: 768

Bravo AF: 0.401

Asia WGS AF: 0.501 AC: 1744 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

Jun 14, 2018

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
Cadd	Benign	1.2
Dann	Benign	0.54

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

LitVar

Other links and lift over

dbSNP: rs10859819; hg19: chr12-95387756;