Genetic Variant NDUFAF1:c.*129_*135delTTTTTTT (chr15-41387308-CAAAAAAA-C) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The ENST00000560978.2(NDUFAF1):c.*129_*135delTTTTTTT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000245 in 572,260 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000015 ( 0 hom., cov: 30)

Exomes 𝑓: 0.000026 ( 0 hom. )

Consequence

NDUFAF1
ENST00000560978.2 3_prime_UTR

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.231

Publications

1 publications found

Variant links:

Genes affected

NDUFAF1 (HGNC:18828): (NADH:ubiquinone oxidoreductase complex assembly factor 1) This gene encodes a complex I assembly factor protein. Complex I (NADH-ubiquinone oxidoreductase) catalyzes the transfer of electrons from NADH to ubiquinone (coenzyme Q) in the first step of the mitochondrial respiratory chain, resulting in the translocation of protons across the inner mitochondrial membrane. The encoded protein is required for assembly of complex I, and mutations in this gene are a cause of mitochondrial complex I deficiency. Alternatively spliced transcript variants have been observed for this gene, and a pseudogene of this gene is located on the long arm of chromosome 19. [provided by RefSeq, Dec 2011]

NDUFAF1 Gene-Disease associations (from GenCC):

mitochondrial disease
Inheritance: AR Classification: MODERATE Submitted by: ClinGen
mitochondrial complex I deficiency
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
mitochondrial complex I deficiency, nuclear type 11
Inheritance: AR Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics

NDUFAF1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000560978.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
NDUFAF1	NM_016013.4	MANE Select	c.129_135delTTTTTTT	downstream_gene	N/A	NP_057097.2
NDUFAF1	NM_001437486.1		c.129_135delTTTTTTT	downstream_gene	N/A	NP_001424415.1
NDUFAF1	NM_001437487.1		c.129_135delTTTTTTT	downstream_gene	N/A	NP_001424416.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
NDUFAF1	ENST00000560978.2	TSL:3	c.129_135delTTTTTTT	3_prime_UTR	Exon 5 of 5	ENSP00000453944.2	Q9Y375
NDUFAF1	ENST00000260361.9	TSL:1 MANE Select	c.129_135delTTTTTTT	downstream_gene	N/A	ENSP00000260361.4	Q9Y375
NDUFAF1	ENST00000559127.5	TSL:1	n.581_587delTTTTTTT	downstream_gene	N/A	ENSP00000453027.1	H0YL22

Frequencies

GnomAD3 genomes

AF:

0.0000150

AC:

AN:

66742

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000571

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000257

AC:

AN:

505518

Hom.:

AF XY:

0.0000224

AC XY:

AN XY:

267650

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

12628

American (AMR)

AF:

0.00

AC:

AN:

18940

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

13428

East Asian (EAS)

AF:

0.00

AC:

AN:

26504

South Asian (SAS)

AF:

0.0000208

AC:

AN:

48054

European-Finnish (FIN)

AF:

0.000199

AC:

AN:

25102

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1876

European-Non Finnish (NFE)

AF:

0.0000180

AC:

AN:

333400

Other (OTH)

AF:

0.0000391

AC:

AN:

25586

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.448

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000150

AC:

AN:

66742

Hom.:

Cov.:

AF XY:

0.0000321

AC XY:

AN XY:

31106

show subpopulations

African (AFR)

AF:

0.0000571

AC:

AN:

17522

American (AMR)

AF:

0.00

AC:

AN:

5812

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

1802

East Asian (EAS)

AF:

0.00

AC:

AN:

2240

South Asian (SAS)

AF:

0.00

AC:

AN:

2212

European-Finnish (FIN)

AF:

0.00

AC:

AN:

3194

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

32570

Other (OTH)

AF:

0.00

AC:

AN:

900

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.23

Splicing

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

15-41387308-CAAAAAAAAAA-CAAA

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over