Variant 16-23596251-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The ENST00000007516.8(NDUFAB1):c.40C>T(p.Pro14Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00033 in 1,597,682 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0017 ( 2 hom., cov: 33)

Exomes 𝑓: 0.00018 ( 1 hom. )

Consequence

NDUFAB1
ENST00000007516.8 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.803

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 Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0070215166).

BP6

Variant 16-23596251-G-A is Benign according to our data. Variant chr16-23596251-G-A is described in ClinVar as [Benign]. Clinvar id is 721858.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NDUFAB1	NM_005003.3 linkuse as main transcript	c.40C>T	p.Pro14Ser	missense_variant	1/5	ENST00000007516.8	NP_004994.1
NDUFAB1	XM_011545856.3 linkuse as main transcript	c.40C>T	p.Pro14Ser	missense_variant	1/6		XP_011544158.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
NDUFAB1	ENST00000007516.8 linkuse as main transcript	c.40C>T	p.Pro14Ser	missense_variant	1/5	1	NM_005003.3	ENSP00000007516	P1
NDUFAB1	ENST00000570319.5 linkuse as main transcript	c.40C>T	p.Pro14Ser	missense_variant	1/4	1		ENSP00000458770	P1
NDUFAB1	ENST00000562133.5 linkuse as main transcript	c.28C>T	p.Pro10Ser	missense_variant	1/4	2		ENSP00000454891
NDUFAB1	ENST00000484769.1 linkuse as main transcript	c.40C>T	p.Pro14Ser	missense_variant, NMD_transcript_variant	1/6	3		ENSP00000454812

Frequencies

GnomAD3 genomes

AF:

0.00171

AC:

261

AN:

152254

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00576

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00118

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:

0.00143

GnomAD3 exomes

AF:

0.000461

AC:

AN:

210596

Hom.:

AF XY:

0.000326

AC XY:

AN XY:

116456

show subpopulations

Gnomad AFR exome

AF:

0.00781

Gnomad AMR exome

AF:

0.000255

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000110

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000183

AC:

265

AN:

1445310

Hom.:

Cov.:

AF XY:

0.000159

AC XY:

114

AN XY:

718302

show subpopulations

Gnomad4 AFR exome

AF:

0.00689

Gnomad4 AMR exome

AF:

0.000352

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000452

Gnomad4 OTH exome

AF:

0.000368

GnomAD4 genome

AF:

0.00172

AC:

262

AN:

152372

Hom.:

Cov.:

AF XY:

0.00166

AC XY:

124

AN XY:

74508

show subpopulations

Gnomad4 AFR

AF:

0.00577

Gnomad4 AMR

AF:

0.00118

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:

0.00142

Alfa

AF:

0.000155

Hom.:

Bravo

AF:

0.00223

ESP6500AA

AF:

0.00376

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000489

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3474

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Apr 10, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.45

CADD

Benign

DANN

Benign

0.86

DEOGEN2

Benign

0.16

T;T

Eigen

Benign

-0.83

Eigen_PC

Benign

-0.76

FATHMM_MKL

Benign

0.54

LIST_S2

Benign

0.69

.;T

MetaRNN

Benign

0.0070

T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

1.6

L;L

MutationTaster

Benign

0.93

N;N

PrimateAI

Uncertain

0.59

PROVEAN

Benign

-0.42

N;.

REVEL

Benign

0.034

Sift

Benign

0.32

T;.

Sift4G

Benign

0.58

T;T

Polyphen

0.0090

B;B

Vest4

0.28

MVP

0.31

MPC

0.29

ClinPred

0.021

GERP RS

0.48

RBP_binding_hub_radar

0.92

RBP_regulation_power_radar

2.1

Varity_R

0.035

gMVP

0.54

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