15-41387294-G-A

Position:

• chr15-41387294-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000560978.2(NDUFAF1):​c.*150C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.219 in 698,590 control chromosomes in the GnomAD database, including 19,385 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.22 (3797 hom., cov: 23)
  • Exomes 𝑓: 0.22 (15588 hom.)
• Consequence: NDUFAF1 ENST00000560978.2 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.243

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BP6: Variant 15-41387294-G-A is Benign according to our data. Variant chr15-41387294-G-A is described in ClinVar as [Benign]. Clinvar id is 1221259.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.257 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
NDUFAF1	ENST00000560978.2	c.*150C>T		3_prime_UTR_variant	5/5	3		ENSP00000453944	P1

Frequencies

GnomAD3 genomes AF: 0.224 AC: 32034 AN: 142868 Hom.: 3800 Cov.: 23

Gnomad AFR AF: 0.174

Gnomad AMI AF: 0.346

Gnomad AMR AF: 0.197

Gnomad ASJ AF: 0.259

Gnomad EAS AF: 0.0144

Gnomad SAS AF: 0.176

Gnomad FIN AF: 0.329

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.261

Gnomad OTH AF: 0.219

GnomAD4 exome AF: 0.218 AC: 121131 AN: 555646 Hom.: 15588 AF XY: 0.217 AC XY: 63943 AN XY: 294228

Gnomad4 AFR exome AF: 0.150

Gnomad4 AMR exome AF: 0.147

Gnomad4 ASJ exome AF: 0.249

Gnomad4 EAS exome AF: 0.0137

Gnomad4 SAS exome AF: 0.184

Gnomad4 FIN exome AF: 0.285

Gnomad4 NFE exome AF: 0.241

Gnomad4 OTH exome AF: 0.218

GnomAD4 genome AF: 0.224 AC: 32029 AN: 142944 Hom.: 3797 Cov.: 23 AF XY: 0.225 AC XY: 15521 AN XY: 68970

Gnomad4 AFR AF: 0.173

Gnomad4 AMR AF: 0.197

Gnomad4 ASJ AF: 0.259

Gnomad4 EAS AF: 0.0143

Gnomad4 SAS AF: 0.176

Gnomad4 FIN AF: 0.329

Gnomad4 NFE AF: 0.261

Gnomad4 OTH AF: 0.219

Alfa AF: 0.242 Hom.: 585

Bravo AF: 0.209

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 10, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	3.0
DANN	Benign	0.25

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs28703570; hg19: chr15-41679492;