NM_016013.4:c.906C>T

Variant names:

• chr15-41387522-G-A
• rs560838828
• NM_016013.4:c.906C>T

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_016013.4(NDUFAF1):​c.906C>T​(p.Gly302Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000158 in 1,612,562 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.000092 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00017 (2 hom.)
• Consequence: NDUFAF1 NM_016013.4 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.493
• 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: Benign. The variant received -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BP6: Variant 15-41387522-G-A is Benign according to our data. Variant chr15-41387522-G-A is described in ClinVar as Benign. ClinVar VariationId is 2187430.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.493 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome4 at 2 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016013.4. 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.906C>T	p.Gly302Gly	synonymous	Exon 5 of 5	NP_057097.2
	NDUFAF1	NM_001437486.1		c.906C>T	p.Gly302Gly	synonymous	Exon 5 of 5	NP_001424415.1
	NDUFAF1	NM_001437487.1		c.906C>T	p.Gly302Gly	synonymous	Exon 5 of 5	NP_001424416.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NDUFAF1	ENST00000260361.9	TSL:1 MANE Select	c.906C>T	p.Gly302Gly	synonymous	Exon 5 of 5	ENSP00000260361.4	Q9Y375
	NDUFAF1	ENST00000559127.5	TSL:1	n.*374C>T		non_coding_transcript_exon	Exon 6 of 6	ENSP00000453027.1	H0YL22
	NDUFAF1	ENST00000559127.5	TSL:1	n.*374C>T		3_prime_UTR	Exon 6 of 6	ENSP00000453027.1	H0YL22

Frequencies

GnomAD3 genomes AF: 0.0000921 AC: 14 AN: 152036 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000121

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00187

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000346 AC: 87 AN: 251404 AF XY: 0.000471

Gnomad AFR exome AF: 0.0000616

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000879

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000165 AC: 241 AN: 1460408 Hom.: 2 Cov.: 31 AF XY: 0.000226 AC XY: 164 AN XY: 726622

African (AFR) AF: 0.000239 AC: 8 AN: 33440

American (AMR) AF: 0.0000224 AC: 1 AN: 44724

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 39662

South Asian (SAS) AF: 0.00254 AC: 219 AN: 86228

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53412

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

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1110692

Other (OTH) AF: 0.000182 AC: 11 AN: 60356

GnomAD4 genome AF: 0.0000920 AC: 14 AN: 152154 Hom.: 0 Cov.: 32 AF XY: 0.000134 AC XY: 10 AN XY: 74364

African (AFR) AF: 0.000120 AC: 5 AN: 41512

American (AMR) AF: 0.00 AC: 0 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.00187 AC: 9 AN: 4816

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10584

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68012

Other (OTH) AF: 0.00 AC: 0 AN: 2108

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000604

Asia WGS AF: 0.000577 AC: 2 AN: 3478

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	3.1
DANN	Benign	0.44
PhyloP100		-0.49
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs560838828; hg19: chr15-41679720; COSMIC: COSV52974730;