12-94994008-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+162G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0708 in 152,150 control chromosomes in the GnomAD database, including 491 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.071 (491 hom., cov: 32)
• Consequence: NDUFA12 NM_018838.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0250

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=-0.6).
• BP6: Variant 12-94994008-C-T is Benign according to our data. Variant chr12-94994008-C-T is described in ClinVar as [Benign]. Clinvar id is 1238629.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.15 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NDUFA12	NM_018838.5	c.257+162G>A		intron_variant		ENST00000327772.7
NDUFA12	NM_001258338.2	c.169+8731G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NDUFA12	ENST00000327772.7	c.257+162G>A		intron_variant		1	NM_018838.5	P1

Frequencies

GnomAD3 genomes AF: 0.0708 AC: 10759 AN: 152030 Hom.: 488 Cov.: 32

Gnomad AFR AF: 0.0286

Gnomad AMI AF: 0.0769

Gnomad AMR AF: 0.106

Gnomad ASJ AF: 0.0882

Gnomad EAS AF: 0.0982

Gnomad SAS AF: 0.159

Gnomad FIN AF: 0.160

Gnomad MID AF: 0.0955

Gnomad NFE AF: 0.0650

Gnomad OTH AF: 0.0750

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

GnomAD4 genome AF: 0.0708 AC: 10766 AN: 152150 Hom.: 491 Cov.: 32 AF XY: 0.0764 AC XY: 5683 AN XY: 74380

Gnomad4 AFR AF: 0.0286

Gnomad4 AMR AF: 0.106

Gnomad4 ASJ AF: 0.0882

Gnomad4 EAS AF: 0.0982

Gnomad4 SAS AF: 0.160

Gnomad4 FIN AF: 0.160

Gnomad4 NFE AF: 0.0650

Gnomad4 OTH AF: 0.0738

Alfa AF: 0.0729 Hom.: 49

Bravo AF: 0.0675

Asia WGS AF: 0.130 AC: 450 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 28, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
Cadd	Benign	8.4
Dann	Benign	0.93

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: rs59732187; hg19: chr12-95387784;