12-94934697-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000552205.6(NDUFA12):​c.258-6434C>A variant causes a intron, NMD transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.245 in 152,144 control chromosomes in the GnomAD database, including 5,138 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 0.24 ( 5138 hom., cov: 33)

Consequence

NDUFA12
ENST00000552205.6 intron, NMD_transcript

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.817
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.89).
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.369 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
NDUFA12ENST00000552205.6 linkuse as main transcriptc.258-6434C>A intron_variant, NMD_transcript_variant 5 ENSP00000449144

Frequencies

GnomAD3 genomes
AF:
0.245
AC:
37205
AN:
152026
Hom.:
5133
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.374
Gnomad AMI
AF:
0.237
Gnomad AMR
AF:
0.187
Gnomad ASJ
AF:
0.185
Gnomad EAS
AF:
0.179
Gnomad SAS
AF:
0.137
Gnomad FIN
AF:
0.159
Gnomad MID
AF:
0.165
Gnomad NFE
AF:
0.209
Gnomad OTH
AF:
0.238
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.245
AC:
37224
AN:
152144
Hom.:
5138
Cov.:
33
AF XY:
0.240
AC XY:
17889
AN XY:
74394
show subpopulations
Gnomad4 AFR
AF:
0.374
Gnomad4 AMR
AF:
0.186
Gnomad4 ASJ
AF:
0.185
Gnomad4 EAS
AF:
0.179
Gnomad4 SAS
AF:
0.137
Gnomad4 FIN
AF:
0.159
Gnomad4 NFE
AF:
0.209
Gnomad4 OTH
AF:
0.238
Alfa
AF:
0.218
Hom.:
3882
Bravo
AF:
0.251
Asia WGS
AF:
0.185
AC:
642
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.89
CADD
Benign
0.23
DANN
Benign
0.80

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs249166; hg19: chr12-95328473; API