rs162235

Positions:

• chr5-61017188-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_174889.5(NDUFAF2):​c.128-55937T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.138 in 152,210 control chromosomes in the GnomAD database, including 1,812 homozygotes. 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: 𝑓 0.14 (1812 hom., cov: 33)
• Consequence: NDUFAF2 NM_174889.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.104

Genes affected

NDUFAF2 (HGNC:28086): (NADH:ubiquinone oxidoreductase complex assembly factor 2) NADH:ubiquinone oxidoreductase (complex I) 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. This gene encodes a complex I assembly factor. Mutations in this gene cause progressive encephalopathy resulting from mitochondrial complex I deficiency. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.267 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NDUFAF2	NM_174889.5	c.128-55937T>C		intron_variant		ENST00000296597.10	NP_777549.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NDUFAF2	ENST00000296597.10	c.128-55937T>C		intron_variant		1	NM_174889.5	ENSP00000296597	P1

Frequencies

GnomAD3 genomes AF: 0.138 AC: 20929 AN: 152092 Hom.: 1806 Cov.: 33

Gnomad AFR AF: 0.0376

Gnomad AMI AF: 0.213

Gnomad AMR AF: 0.145

Gnomad ASJ AF: 0.150

Gnomad EAS AF: 0.137

Gnomad SAS AF: 0.280

Gnomad FIN AF: 0.200

Gnomad MID AF: 0.212

Gnomad NFE AF: 0.175

Gnomad OTH AF: 0.134

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.138 AC: 20947 AN: 152210 Hom.: 1812 Cov.: 33 AF XY: 0.141 AC XY: 10501 AN XY: 74402

Gnomad4 AFR AF: 0.0378

Gnomad4 AMR AF: 0.145

Gnomad4 ASJ AF: 0.150

Gnomad4 EAS AF: 0.137

Gnomad4 SAS AF: 0.280

Gnomad4 FIN AF: 0.200

Gnomad4 NFE AF: 0.175

Gnomad4 OTH AF: 0.141

Alfa AF: 0.172 Hom.: 1151

Bravo AF: 0.125

Asia WGS AF: 0.209 AC: 725 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	6.2
DANN	Benign	0.79

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

Publications

LitVar

Other links and lift over

dbSNP: rs162235; hg19: chr5-60313015; COSMIC: COSV56943772;