rs377540343

Variant names:

• chr17-81239391-C-A
• NM_001086521.2:c.28C>A

Your query was ambiguous. Multiple possible variants found:

• chr17-81239391-C-A
• chr17-81239391-C-G
• chr17-81239391-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001086521.2(NDUFAF8):​c.28C>A​(p.Arg10Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000165 in 1,215,742 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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. R10C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000016 (0 hom.)
• Consequence: NDUFAF8 NM_001086521.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.16

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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.782

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NDUFAF8	NM_001086521.2	c.28C>A	p.Arg10Ser	missense_variant	Exon 1 of 3	ENST00000431388.3	NP_001079990.1
NDUFAF8	NM_001353402.1	c.28C>A	p.Arg10Ser	missense_variant	Exon 1 of 3		NP_001340331.1
NDUFAF8	NM_001353403.1	c.-396C>A		5_prime_UTR_variant	Exon 1 of 3		NP_001340332.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NDUFAF8	ENST00000431388.3	c.28C>A	p.Arg10Ser	missense_variant	Exon 1 of 3	1	NM_001086521.2	ENSP00000400184.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000165 AC: 2 AN: 1215742 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 586084

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: 0.0000235

Gnomad4 NFE exome AF: 0.00000101

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.43
BayesDel_addAF	Pathogenic	0.17	D
BayesDel_noAF	Uncertain	0.010
CADD	Pathogenic	26
DANN	Benign	0.97
DEOGEN2	Benign	0.041	T
Eigen	Benign	0.14
Eigen_PC	Benign	0.14
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.61	T
M_CAP	Pathogenic	0.39	D
MetaRNN	Pathogenic	0.78	D
MetaSVM	Benign	-0.64	T
PROVEAN	Benign	-2.3	N
REVEL	Benign	0.15
Sift	Benign	0.071	T
Sift4G	Benign	0.093	T
Polyphen		0.79	P
Vest4		0.76
MutPred		0.25		Loss of methylation at R10 (P = 0.0152);
MVP		0.17
MPC		0.87
ClinPred		0.90	D
GERP RS		3.8
RBP_binding_hub_radar		1.0
RBP_regulation_power_radar		2.7
Varity_R		0.29
gMVP		0.51

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: chr17-79213191;