rs1007712101

Variant names:

• chr17-81239382-G-A
• NM_001086521.2:c.19G>A

Your query was ambiguous. Multiple possible variants found:

• chr17-81239382-G-A
• chr17-81239382-G-C
• chr17-81239382-G-T

Variant summary

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

The NM_001353403.1(NDUFAF8):​c.-405G>A variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000821 in 1,218,188 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 8.2e-7 (0 hom.)
• Consequence: NDUFAF8 NM_001353403.1 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.02

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NDUFAF8	NM_001086521.2	c.19G>A	p.Val7Met	missense_variant	Exon 1 of 3	ENST00000431388.3	NP_001079990.1
NDUFAF8	NM_001353403.1	c.-405G>A		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 3		NP_001340332.1
NDUFAF8	NM_001353402.1	c.19G>A	p.Val7Met	missense_variant	Exon 1 of 3		NP_001340331.1
NDUFAF8	NM_001353403.1	c.-405G>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.19G>A	p.Val7Met	missense_variant	Exon 1 of 3	1	NM_001086521.2	ENSP00000400184.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 8.21e-7 AC: 1 AN: 1218188 Hom.: 0 Cov.: 31 AF XY: 0.00000170 AC XY: 1 AN XY: 587358

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: 0.0000194

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

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	0.47
BayesDel_addAF	Uncertain	0.064	T
BayesDel_noAF	Benign	-0.15
CADD	Uncertain	23
DANN	Benign	0.91
DEOGEN2	Benign	0.026	T
Eigen	Uncertain	0.20
Eigen_PC	Benign	0.12
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.66	T
M_CAP	Pathogenic	0.52	D
MetaRNN	Uncertain	0.44	T
MetaSVM	Benign	-0.35	T
PROVEAN	Benign	-0.93	N
REVEL	Benign	0.14
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.96	D
Vest4		0.40
MutPred		0.31		Gain of disorder (P = 0.0251);
MVP		0.061
MPC		0.67
ClinPred		0.87	D
GERP RS		3.8
RBP_binding_hub_radar		1.0
RBP_regulation_power_radar		2.7
Varity_R		0.21
gMVP		0.55

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: chr17-79213182;