rs7965624

Variant names:

• chr12-94907877-A-G
• rs7965624
• ENST00000547447.1:n.272+2356T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000547447.1(NDUFA12):​n.272+2356T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.579 in 152,012 control chromosomes in the GnomAD database, including 25,931 homozygotes. 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: 𝑓 0.58 (25931 hom., cov: 32)
• Consequence: NDUFA12 ENST00000547447.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.808
• Publications: 5 publications found

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]

NDUFA12 Gene-Disease associations (from GenCC):

• mitochondrial complex I deficiency, nuclear type 23

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P
• Leigh syndrome with leukodystrophy

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• Leigh syndrome

  Inheritance: AR Classification: LIMITED Submitted by: ClinGen

LOC105369915 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.627 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000547447.1. 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NDUFA12	ENST00000547447.1	TSL:3	n.272+2356T>C		intron	N/A
	NDUFA12	ENST00000552205.6	TSL:5	n.*180-10567T>C		intron	N/A	ENSP00000449144.2	H0YID5

Frequencies

GnomAD3 genomes AF: 0.579 AC: 87938 AN: 151894 Hom.: 25899 Cov.: 32

Gnomad AFR AF: 0.534

Gnomad AMI AF: 0.521

Gnomad AMR AF: 0.591

Gnomad ASJ AF: 0.609

Gnomad EAS AF: 0.305

Gnomad SAS AF: 0.521

Gnomad FIN AF: 0.551

Gnomad MID AF: 0.573

Gnomad NFE AF: 0.632

Gnomad OTH AF: 0.581

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

GnomAD4 genome AF: 0.579 AC: 88022 AN: 152012 Hom.: 25931 Cov.: 32 AF XY: 0.577 AC XY: 42827 AN XY: 74276

African (AFR) AF: 0.535 AC: 22155 AN: 41446

American (AMR) AF: 0.590 AC: 9016 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.609 AC: 2112 AN: 3468

East Asian (EAS) AF: 0.306 AC: 1577 AN: 5162

South Asian (SAS) AF: 0.522 AC: 2510 AN: 4808

European-Finnish (FIN) AF: 0.551 AC: 5827 AN: 10566

Middle Eastern (MID) AF: 0.568 AC: 167 AN: 294

European-Non Finnish (NFE) AF: 0.632 AC: 42947 AN: 67970

Other (OTH) AF: 0.586 AC: 1236 AN: 2108

Alfa AF: 0.611 Hom.: 96969

Bravo AF: 0.576

Asia WGS AF: 0.488 AC: 1700 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.44
DANN	Benign	0.29
PhyloP100		-0.81

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs7965624;

hg19: chr12-95301653;