15-41387308-C-CA

Position:

• chr15-41387308-C-CA

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The ENST00000560978.2(NDUFAF1):​c.*135_*136insT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0779 in 566,786 control chromosomes in the GnomAD database, including 22 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.020 (22 hom., cov: 30)
  • Exomes 𝑓: 0.086 (0 hom.)
• Consequence: NDUFAF1 ENST00000560978.2 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.231

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]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 15-41387308-C-CA is Benign according to our data. Variant chr15-41387308-C-CA is described in ClinVar as [Benign]. Clinvar id is 1228185.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0525 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NDUFAF1	NM_016013.4			downstream_gene_variant		ENST00000260361.9	NP_057097.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NDUFAF1	ENST00000560978.2	c.*135_*136insT		3_prime_UTR_variant	5/5	3		ENSP00000453944	P1
NDUFAF1	ENST00000260361.9			downstream_gene_variant		1	NM_016013.4	ENSP00000260361	P1
NDUFAF1	ENST00000676906.1			downstream_gene_variant				ENSP00000503122

Frequencies

GnomAD3 genomes AF: 0.0204 AC: 1357 AN: 66408 Hom.: 21 Cov.: 30

Gnomad AFR AF: 0.0554

Gnomad AMI AF: 0.00253

Gnomad AMR AF: 0.0117

Gnomad ASJ AF: 0.00167

Gnomad EAS AF: 0.0327

Gnomad SAS AF: 0.0104

Gnomad FIN AF: 0.00595

Gnomad MID AF: 0.106

Gnomad NFE AF: 0.00525

Gnomad OTH AF: 0.0268

GnomAD3 exomes AF: 0.0671 AC: 2785 AN: 41530 Hom.: 0 AF XY: 0.0651 AC XY: 1409 AN XY: 21656

Gnomad AFR exome AF: 0.104

Gnomad AMR exome AF: 0.0672

Gnomad ASJ exome AF: 0.0553

Gnomad EAS exome AF: 0.0734

Gnomad SAS exome AF: 0.0562

Gnomad FIN exome AF: 0.0242

Gnomad NFE exome AF: 0.0644

Gnomad OTH exome AF: 0.0724

GnomAD4 exome AF: 0.0855 AC: 42787 AN: 500360 Hom.: 0 Cov.: 0 AF XY: 0.0853 AC XY: 22583 AN XY: 264772

Gnomad4 AFR exome AF: 0.108

Gnomad4 AMR exome AF: 0.0714

Gnomad4 ASJ exome AF: 0.0812

Gnomad4 EAS exome AF: 0.0944

Gnomad4 SAS exome AF: 0.0627

Gnomad4 FIN exome AF: 0.0750

Gnomad4 NFE exome AF: 0.0888

Gnomad4 OTH exome AF: 0.0875

GnomAD4 genome AF: 0.0205 AC: 1359 AN: 66426 Hom.: 22 Cov.: 30 AF XY: 0.0210 AC XY: 650 AN XY: 30974

Gnomad4 AFR AF: 0.0553

Gnomad4 AMR AF: 0.0117

Gnomad4 ASJ AF: 0.00167

Gnomad4 EAS AF: 0.0329

Gnomad4 SAS AF: 0.0105

Gnomad4 FIN AF: 0.00595

Gnomad4 NFE AF: 0.00523

Gnomad4 OTH AF: 0.0286

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

Aug 06, 2019

- -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs751327964; hg19: chr15-41679506;