3-49022170-G-A

Variant names:

• chr3-49022170-G-A
• NM_199069.2:c.26G>A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_199069.2(NDUFAF3):​c.26G>A​(p.Ser9Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,457,964 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict 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: 6.9e-7 (0 hom.)
• Consequence: NDUFAF3 NM_199069.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.64

Genes affected

NDUFAF3 (HGNC:29918): (NADH:ubiquinone oxidoreductase complex assembly factor 3) This gene encodes a mitochondrial complex I assembly protein that interacts with complex I subunits. Mutations in this gene cause mitochondrial complex I deficiency, a fatal neonatal disorder of the oxidative phosphorylation system. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2009]

DALRD3 (HGNC:25536): (DALR anticodon binding domain containing 3) The exact function of this gene is not known. It encodes a protein with a DALR anticodon binding domain similar to that of class Ia aminoacyl tRNA synthetases. This gene is located in a cluster of genes (with a complex sense-anti-sense genome architecture) on chromosome 3, and contains two micro RNA (miRNA) precursors (mir-425 and mir-191) in one of its introns. Preferential expression of this gene (the miRNAs and other genes in the cluster) in testis suggests a role of this gene in spermatogenesis (PMID:19906709). [provided by RefSeq, Feb 2013]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.03866121).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NDUFAF3	NM_199069.2	c.26G>A	p.Ser9Asn	missense_variant	Exon 1 of 5	ENST00000326925.11	NP_951032.1
NDUFAF3	NM_199070.2	c.-94-176G>A		intron_variant	Intron 1 of 4		NP_951033.1
NDUFAF3	NM_199073.2	c.-94-176G>A		intron_variant	Intron 1 of 4		NP_951047.1
NDUFAF3	NM_199074.2	c.-94-176G>A		intron_variant	Intron 1 of 4		NP_951056.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NDUFAF3	ENST00000326925.11	c.26G>A	p.Ser9Asn	missense_variant	Exon 1 of 5	1	NM_199069.2	ENSP00000323076.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.86e-7 AC: 1 AN: 1457964 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 725466

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.00e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	1.0
DANN	Benign	0.81
DEOGEN2	Benign	0.026	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.039	N
LIST_S2	Benign	0.24	T
M_CAP	Benign	0.039	D
MetaRNN	Benign	0.039	T
MetaSVM	Benign	-0.71	T
MutationAssessor	Benign	0.20	N
PrimateAI	Uncertain	0.57	T
PROVEAN	Benign	-0.65	N
REVEL	Benign	0.11
Sift	Benign	0.31	T
Sift4G	Benign	0.26	T
Polyphen		0.0	B
Vest4		0.055
MutPred		0.22		Gain of glycosylation at S9 (P = 0.0169);
MVP		0.28
MPC		0.45
ClinPred		0.053	T
GERP RS		-1.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.054
gMVP		0.30

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-49059603;