8-95024928-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001354516.2(NDUFAF6):c.42-7067A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.14 in 1,185,828 control chromosomes in the GnomAD database, including 11,935 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.15 (1642 hom., cov: 33)
  • Exomes 𝑓: 0.14 (10293 hom.)
• Consequence: NDUFAF6 NM_001354516.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.671

Genes affected

NDUFAF6 (HGNC:28625): (NADH:ubiquinone oxidoreductase complex assembly factor 6) This gene encodes a protein that localizes to mitochondria and contains a predicted phytoene synthase domain. The encoded protein plays an important role in the assembly of complex I (NADH-ubiquinone oxidoreductase) of the mitochondrial respiratory chain through regulation of subunit ND1 biogenesis. Mutations in this gene are associated with complex I enzymatic deficiency. [provided by RefSeq, Nov 2011]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 8-95024928-A-G is Benign according to our data. Variant chr8-95024928-A-G is described in ClinVar as [Benign]. Clinvar id is 1292143.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.158 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NDUFAF6	NM_001354514.2	c.-83-7067A>G		intron_variant
NDUFAF6	NM_001354515.2	c.-83-7067A>G		intron_variant
NDUFAF6	NM_001354516.2	c.42-7067A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NDUFAF6	ENST00000396111.6	c.-83-7067A>G		intron_variant		5
NDUFAF6	ENST00000396113.5	c.-84+1609A>G		intron_variant		5
NDUFAF6	ENST00000519136.5	c.-255-7067A>G		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.146 AC: 22214 AN: 152036 Hom.: 1641 Cov.: 33

Gnomad AFR AF: 0.162

Gnomad AMI AF: 0.0669

Gnomad AMR AF: 0.130

Gnomad ASJ AF: 0.128

Gnomad EAS AF: 0.0590

Gnomad SAS AF: 0.125

Gnomad FIN AF: 0.174

Gnomad MID AF: 0.222

Gnomad NFE AF: 0.146

Gnomad OTH AF: 0.146

GnomAD4 exome AF: 0.139 AC: 143829 AN: 1033674 Hom.: 10293 AF XY: 0.139 AC XY: 68504 AN XY: 494170

Gnomad4 AFR exome AF: 0.165

Gnomad4 AMR exome AF: 0.114

Gnomad4 ASJ exome AF: 0.132

Gnomad4 EAS exome AF: 0.0501

Gnomad4 SAS exome AF: 0.120

Gnomad4 FIN exome AF: 0.173

Gnomad4 NFE exome AF: 0.141

Gnomad4 OTH exome AF: 0.135

GnomAD4 genome AF: 0.146 AC: 22228 AN: 152154 Hom.: 1642 Cov.: 33 AF XY: 0.148 AC XY: 10996 AN XY: 74396

Gnomad4 AFR AF: 0.162

Gnomad4 AMR AF: 0.130

Gnomad4 ASJ AF: 0.128

Gnomad4 EAS AF: 0.0592

Gnomad4 SAS AF: 0.124

Gnomad4 FIN AF: 0.174

Gnomad4 NFE AF: 0.146

Gnomad4 OTH AF: 0.145

Alfa AF: 0.154 Hom.: 221

Bravo AF: 0.143

Asia WGS AF: 0.0910 AC: 319 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 26, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	4.6
Dann	Benign	0.27

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs77790737; hg19: chr8-96037156;