dbSNP rs1007712101: NDUFAF8:p.Val7Leu (chr17-81239382-G-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001353403.1(NDUFAF8):c.-405G>T 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 0.0000124 in 1,370,434 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000092 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000025 ( 0 hom. )

Consequence

NDUFAF8
NM_001353403.1 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.02

Publications

0 publications found

Variant links:

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]

NDUFAF8 Gene-Disease associations (from GenCC):

mitochondrial complex I deficiency, nuclear type 34
Inheritance: AR Classification: STRONG, MODERATE Submitted by: G2P, Ambry Genetics
Leigh syndrome
Inheritance: AR Classification: MODERATE Submitted by: ClinGen
mitochondrial complex I deficiency
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

NDUFAF8 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.20093933).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001353403.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NDUFAF8	NM_001086521.2	MANE Select	c.19G>T	p.Val7Leu	missense	Exon 1 of 3	NP_001079990.1	A1L188
NDUFAF8	NM_001353403.1		c.-405G>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 3	NP_001340332.1
NDUFAF8	NM_001353402.1		c.19G>T	p.Val7Leu	missense	Exon 1 of 3	NP_001340331.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NDUFAF8	ENST00000431388.3	TSL:1 MANE Select	c.19G>T	p.Val7Leu	missense	Exon 1 of 3	ENSP00000400184.2	A1L188
NDUFAF8	ENST00000577158.2	TSL:1	n.78G>T		non_coding_transcript_exon	Exon 1 of 3
NDUFAF8	ENST00000573090.1	TSL:3	n.72G>T		non_coding_transcript_exon	Exon 1 of 3

Frequencies

GnomAD3 genomes

AF:

0.0000920

AC:

AN:

152246

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000338

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00

AC:

AN:

17320

AF XY:

0.00

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000246

AC:

AN:

1218188

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

587358

show subpopulations

African (AFR)

AF:

0.0000426

AC:

AN:

23488

American (AMR)

AF:

0.00

AC:

AN:

9790

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

16722

East Asian (EAS)

AF:

0.00

AC:

AN:

27336

South Asian (SAS)

AF:

0.00

AC:

AN:

51522

European-Finnish (FIN)

AF:

0.00

AC:

AN:

42802

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3370

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

993410

Other (OTH)

AF:

0.0000402

AC:

AN:

49748

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000920

AC:

AN:

152246

Hom.:

Cov.:

AF XY:

0.000121

AC XY:

AN XY:

74384

show subpopulations

African (AFR)

AF:

0.000338

AC:

AN:

41472

American (AMR)

AF:

0.00

AC:

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.00

AC:

AN:

4838

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10630

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68036

Other (OTH)

AF:

0.00

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.471

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.0000604

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.29

BayesDel_addAF

Benign

0.011

BayesDel_noAF

Benign

-0.22

CADD

Benign

(source)

DANN

Benign

0.83

DEOGEN2

Benign

0.024

Eigen

Benign

-0.28

Eigen_PC

Benign

-0.22

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.58

M_CAP

Uncertain

0.29

MetaRNN

Benign

0.20

MetaSVM

Benign

-0.73

PhyloP100

2.0

PROVEAN

Benign

-1.4

REVEL

Benign

0.11

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

0.022

Vest4

0.23

MutPred

0.23

Loss of sheet (P = 0.0228)

MVP

0.040

MPC

0.23

ClinPred

0.88

GERP RS

3.8

PromoterAI

0.041

Neutral

(source)

Varity_R

0.27

gMVP

0.51

Mutation Taster

=99/1

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over