rs141408814

Variant names:

• chr15-41387534-T-A
• rs141408814
• NM_016013.4:c.894A>T

Your query was ambiguous. Multiple possible variants found:

• chr15-41387534-T-A
• chr15-41387534-T-C
• chr15-41387534-T-G

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PM4

The NM_001437488.1(NDUFAF1):​c.881A>T​(p.Ter294Leuext*?) variant causes a stop lost change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,460,628 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: NDUFAF1 NM_001437488.1 stop_lost
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0410
• Publications: 0 publications found

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

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM4: Stoplost variant in NM_001437488.1 Downstream stopcodon found after 17 codons.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001437488.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NDUFAF1	NM_016013.4	MANE Select	c.894A>T	p.Ile298Ile	synonymous	Exon 5 of 5	NP_057097.2
	NDUFAF1	NM_001437488.1		c.881A>T	p.Ter294Leuext*?	stop_lost	Exon 5 of 5	NP_001424417.1
	NDUFAF1	NM_001437489.1		c.881A>T	p.Ter294Leuext*?	stop_lost	Exon 5 of 5	NP_001424418.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NDUFAF1	ENST00000260361.9	TSL:1 MANE Select	c.894A>T	p.Ile298Ile	synonymous	Exon 5 of 5	ENSP00000260361.4	Q9Y375
	NDUFAF1	ENST00000559127.5	TSL:1	n.*362A>T		non_coding_transcript_exon	Exon 6 of 6	ENSP00000453027.1	H0YL22
	NDUFAF1	ENST00000559127.5	TSL:1	n.*362A>T		3_prime_UTR	Exon 6 of 6	ENSP00000453027.1	H0YL22

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1460628 Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2 AN XY: 726702

African (AFR) AF: 0.00 AC: 0 AN: 33462

American (AMR) AF: 0.00 AC: 0 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26126

East Asian (EAS) AF: 0.00 AC: 0 AN: 39666

South Asian (SAS) AF: 0.00 AC: 0 AN: 86238

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53414

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1110884

Other (OTH) AF: 0.00 AC: 0 AN: 60352

GnomAD4 genome Cov.: 32

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.48
CADD	Benign	7.1
DANN	Benign	0.68
PhyloP100		0.041

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs141408814; hg19: chr15-41679732;