Variant 16-23596275-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_005003.3(NDUFAB1):c.16C>T(p.Leu6Phe) variant causes a missense change. The variant allele was found at a frequency of 0.00000635 in 1,574,284 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000063 ( 0 hom. )

Consequence

NDUFAB1
NM_005003.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.42

Variant links:

Genes affected

NDUFAB1 (HGNC:7694): (NADH:ubiquinone oxidoreductase subunit AB1) Predicted to enable acyl binding activity; acyl carrier activity; and fatty acid binding activity. Involved in mitochondrial respiratory chain complex I assembly and protein lipoylation. Located in mitochondrion and nucleoplasm. Part of mitochondrial respiratory chain complex I. Colocalizes with mitochondrial large ribosomal subunit. [provided by Alliance of Genome Resources, Apr 2022]

NDUFAB1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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/exons	MANE	UniProt
NDUFAB1	NM_005003.3 linkuse as main transcript	c.16C>T	p.Leu6Phe	missense_variant	1/5	ENST00000007516.8
NDUFAB1	XM_011545856.3 linkuse as main transcript	c.16C>T	p.Leu6Phe	missense_variant	1/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
NDUFAB1	ENST00000007516.8 linkuse as main transcript	c.16C>T	p.Leu6Phe	missense_variant	1/5	1	NM_005003.3	P1
NDUFAB1	ENST00000570319.5 linkuse as main transcript	c.16C>T	p.Leu6Phe	missense_variant	1/4	1		P1
NDUFAB1	ENST00000562133.5 linkuse as main transcript	c.4C>T	p.Leu2Phe	missense_variant	1/4	2
NDUFAB1	ENST00000484769.1 linkuse as main transcript	c.16C>T	p.Leu6Phe	missense_variant, NMD_transcript_variant	1/6	3

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152220

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000574

AC:

AN:

174338

Hom.:

AF XY:

0.0000104

AC XY:

AN XY:

96204

show subpopulations

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 SAS exome

AF:

0.0000398

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000633

AC:

AN:

1422064

Hom.:

Cov.:

AF XY:

0.00000567

AC XY:

AN XY:

705042

show subpopulations

Gnomad4 AFR exome

AF:

0.000129

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000122

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.14e-7

Gnomad4 OTH exome

AF:

0.0000509

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152220

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74366

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

ExAC

AF:

0.00000858

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3474

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 03, 2022

The c.16C>T (p.L6F) alteration is located in exon 1 (coding exon 1) of the NDUFAB1 gene. This alteration results from a C to T substitution at nucleotide position 16, causing the leucine (L) at amino acid position 6 to be replaced by a phenylalanine (F). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Uncertain

0.029

BayesDel_noAF

Benign

-0.20

Cadd

Pathogenic

Dann

Uncertain

0.99

DEOGEN2

Benign

0.34

T;T

Eigen

Uncertain

0.20

Eigen_PC

Benign

0.080

FATHMM_MKL

Uncertain

0.89

M_CAP

Benign

0.018

MetaRNN

Uncertain

0.51

D;D

MetaSVM

Benign

-0.36

MutationAssessor

Uncertain

2.2

M;M

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.77

PROVEAN

Benign

-1.7

N;.

REVEL

Uncertain

0.41

Sift

Pathogenic

0.0

D;.

Sift4G

Uncertain

0.012

D;D

Polyphen

1.0

D;D

Vest4

0.50

MutPred

0.36

Loss of helix (P = 0.0104);Loss of helix (P = 0.0104);

MVP

0.52

MPC

0.97

ClinPred

0.97

GERP RS

2.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.2

Varity_R

0.61

gMVP

0.46

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