Genetic Variant NDUFAF6:c.477+146C>T (chr8-95041772-C-T) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_152416.4(NDUFAF6):c.477+146C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.473 in 711,900 control chromosomes in the GnomAD database, including 82,625 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.43 ( 14677 hom., cov: 31)

Exomes 𝑓: 0.48 ( 67948 hom. )

Consequence

NDUFAF6
NM_152416.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.0330

Variant links:

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]

NDUFAF6 links:

ENSG00000287322 (HGNC:):

ENSG00000287322 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant 8-95041772-C-T is Benign according to our data. Variant chr8-95041772-C-T is described in ClinVar as [Benign]. Clinvar id is 1181913.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.67 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NDUFAF6	NM_152416.4 link	c.477+146C>T		intron_variant	Intron 4 of 8	ENST00000396124.9	NP_689629.2	Q330K2-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NDUFAF6	ENST00000396124.9 link	c.477+146C>T		intron_variant	Intron 4 of 8	2	NM_152416.4	ENSP00000379430.4		Q330K2-1

Frequencies

GnomAD3 genomes

AF:

0.429

AC:

65152

AN:

151796

Hom.:

14676

Cov.:

show subpopulations

Gnomad AFR

AF:

0.295

Gnomad AMI

AF:

0.531

Gnomad AMR

AF:

0.497

Gnomad ASJ

AF:

0.500

Gnomad EAS

AF:

0.690

Gnomad SAS

AF:

0.558

Gnomad FIN

AF:

0.450

Gnomad MID

AF:

0.446

Gnomad NFE

AF:

0.457

Gnomad OTH

AF:

0.453

GnomAD4 exome

AF:

0.485

AC:

271528

AN:

559986

Hom.:

67948

AF XY:

0.491

AC XY:

147738

AN XY:

301152

show subpopulations

Gnomad4 AFR exome

AF:

0.290

Gnomad4 AMR exome

AF:

0.538

Gnomad4 ASJ exome

AF:

0.499

Gnomad4 EAS exome

AF:

0.687

Gnomad4 SAS exome

AF:

0.565

Gnomad4 FIN exome

AF:

0.453

Gnomad4 NFE exome

AF:

0.459

Gnomad4 OTH exome

AF:

0.478

GnomAD4 genome

AF:

0.429

AC:

65187

AN:

151914

Hom.:

14677

Cov.:

AF XY:

0.434

AC XY:

32196

AN XY:

74240

show subpopulations

Gnomad4 AFR

AF:

0.295

Gnomad4 AMR

AF:

0.497

Gnomad4 ASJ

AF:

0.500

Gnomad4 EAS

AF:

0.689

Gnomad4 SAS

AF:

0.560

Gnomad4 FIN

AF:

0.450

Gnomad4 NFE

AF:

0.457

Gnomad4 OTH

AF:

0.454

Alfa

AF:

0.434

Hom.:

2690

Bravo

AF:

0.429

Asia WGS

AF:

0.564

AC:

1961

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 23, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

6.2

DANN

Benign

0.54

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over