17-81239653-C-G

Variant names:

• chr17-81239653-C-G
• NM_001086521.2:c.170C>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001086521.2(NDUFAF8):​c.170C>G​(p.Ala57Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000721 in 1,387,730 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A57D) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: NDUFAF8 NM_001086521.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.95

Genes affected

NDUFAF8 (HGNC:33551): (NADH:ubiquinone oxidoreductase complex assembly factor 8) Involved in mitochondrial respiratory chain complex I assembly. Located in mitochondrion. Implicated in nuclear type mitochondrial complex I deficiency 34. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.21709153).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NDUFAF8	NM_001086521.2	c.170C>G	p.Ala57Gly	missense_variant	Exon 2 of 3	ENST00000431388.3	NP_001079990.1
NDUFAF8	NM_001353402.1	c.170C>G	p.Ala57Gly	missense_variant	Exon 2 of 3		NP_001340331.1
NDUFAF8	NM_001353403.1	c.-254C>G		5_prime_UTR_variant	Exon 2 of 3		NP_001340332.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NDUFAF8	ENST00000431388.3	c.170C>G	p.Ala57Gly	missense_variant	Exon 2 of 3	1	NM_001086521.2	ENSP00000400184.2

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 7.21e-7 AC: 1 AN: 1387730 Hom.: 0 Cov.: 34 AF XY: 0.00000146 AC XY: 1 AN XY: 684686

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: 0.0000126

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.0079	T
BayesDel_noAF	Benign	-0.25
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.22	T
Eigen	Benign	-0.018
Eigen_PC	Benign	-0.0097
FATHMM_MKL	Benign	0.47	N
LIST_S2	Uncertain	0.86	D
M_CAP	Pathogenic	0.33	D
MetaRNN	Benign	0.22	T
MetaSVM	Benign	-0.94	T
PROVEAN	Uncertain	-2.9	D
REVEL	Benign	0.049
Sift	Uncertain	0.012	D
Sift4G	Uncertain	0.059	T
Polyphen		0.56	P
Vest4		0.37
MutPred		0.29		Loss of helix (P = 0.0041);
MVP		0.13
MPC		0.82
ClinPred		0.90	D
GERP RS		3.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.21
gMVP		0.35

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-79213453;