15-41387308-CAA-C

Position:

• chr15-41387308-CAA-C

Variant summary

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

The ENST00000560978.2(NDUFAF1):​c.*134_*135del variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.043 in 539,804 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.00079 (0 hom., cov: 30)
  • Exomes 𝑓: 0.049 (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-CAA-C is Benign according to our data. Variant chr15-41387308-CAA-C is described in ClinVar as [Benign]. Clinvar id is 1238975.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAdExome4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0513 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.*134_*135del		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: 0.000795 AC: 53 AN: 66678 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.00183

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000860

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00134

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00253

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000154

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.0696 AC: 2891 AN: 41530 Hom.: 0 AF XY: 0.0702 AC XY: 1520 AN XY: 21656

Gnomad AFR exome AF: 0.0651

Gnomad AMR exome AF: 0.0821

Gnomad ASJ exome AF: 0.0566

Gnomad EAS exome AF: 0.0806

Gnomad SAS exome AF: 0.0734

Gnomad FIN exome AF: 0.0249

Gnomad NFE exome AF: 0.0644

Gnomad OTH exome AF: 0.0777

GnomAD4 exome AF: 0.0490 AC: 23179 AN: 473108 Hom.: 0 AF XY: 0.0481 AC XY: 12024 AN XY: 250046

Gnomad4 AFR exome AF: 0.0442

Gnomad4 AMR exome AF: 0.0542

Gnomad4 ASJ exome AF: 0.0507

Gnomad4 EAS exome AF: 0.0514

Gnomad4 SAS exome AF: 0.0484

Gnomad4 FIN exome AF: 0.0537

Gnomad4 NFE exome AF: 0.0481

Gnomad4 OTH exome AF: 0.0522

GnomAD4 genome AF: 0.000795 AC: 53 AN: 66696 Hom.: 0 Cov.: 30 AF XY: 0.000739 AC XY: 23 AN XY: 31104

Gnomad4 AFR AF: 0.00182

Gnomad4 AMR AF: 0.000860

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00135

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00253

Gnomad4 NFE AF: 0.000154

Gnomad4 OTH AF: 0.00

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 13, 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;