Variant 19-19516312-T-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_015965.7(NDUFA13):c.74T>G(p.Leu25Trp) variant causes a missense change. The variant allele was found at a frequency of 0.000517 in 1,613,342 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.00061 ( 2 hom., cov: 33)

Exomes 𝑓: 0.00051 ( 5 hom. )

Consequence

NDUFA13
NM_015965.7 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:2

Conservation

PhyloP100: 6.34

Variant links:

Genes affected

NDUFA13 (HGNC:17194): (NADH:ubiquinone oxidoreductase subunit A13) This gene encodes a subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (Complex I), which functions in the transfer of electrons from NADH to the respiratory chain. The protein is required for complex I assembly and electron transfer activity. The protein binds the signal transducers and activators of transcription 3 (STAT3) transcription factor, and can function as a tumor suppressor. The human protein purified from mitochondria migrates at approximately 16 kDa. Transcripts originating from an upstream promoter and capable of expressing a protein with a longer N-terminus have been found, but their biological validity has not been determined. [provided by RefSeq, Oct 2009]

NDUFA13 links:

ENSG00000258674 (HGNC:):

ENSG00000258674 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=0.014015585).

BP6

Variant 19-19516312-T-G is Benign according to our data. Variant chr19-19516312-T-G is described in ClinVar as [Benign]. Clinvar id is 2155286.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 92 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NDUFA13	NM_015965.7 linkuse as main transcript	c.74T>G	p.Leu25Trp	missense_variant	1/5	ENST00000507754.9	NP_057049.5	Q9P0J0-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NDUFA13	ENST00000507754.9 linkuse as main transcript	c.74T>G	p.Leu25Trp	missense_variant	1/5	1	NM_015965.7	ENSP00000423673.1		Q9P0J0-1
ENSG00000258674	ENST00000555938.1 linkuse as main transcript	c.74T>G	p.Leu25Trp	missense_variant	1/7	2		ENSP00000452549.1		E7ENQ6

Frequencies

GnomAD3 genomes

AF:

0.000606

AC:

AN:

151916

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000726

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000590

Gnomad ASJ

AF:

0.0199

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000883

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.000964

AC:

241

AN:

249984

Hom.:

AF XY:

0.000848

AC XY:

115

AN XY:

135616

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000434

Gnomad ASJ exome

AF:

0.0191

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000222

Gnomad OTH exome

AF:

0.00148

GnomAD4 exome

AF:

0.000508

AC:

742

AN:

1461426

Hom.:

Cov.:

AF XY:

0.000519

AC XY:

377

AN XY:

727010

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.000447

Gnomad4 ASJ exome

AF:

0.0210

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000189

Gnomad4 NFE exome

AF:

0.0000800

Gnomad4 OTH exome

AF:

0.00134

GnomAD4 genome

AF:

0.000606

AC:

AN:

151916

Hom.:

Cov.:

AF XY:

0.000701

AC XY:

AN XY:

74194

show subpopulations

Gnomad4 AFR

AF:

0.0000726

Gnomad4 AMR

AF:

0.000590

Gnomad4 ASJ

AF:

0.0199

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000883

Gnomad4 OTH

AF:

0.00239

Alfa

AF:

0.00113

Hom.:

Bravo

AF:

0.000782

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.00163

AC:

ExAC

AF:

0.000634

AC:

EpiCase

AF:

0.000436

EpiControl

AF:

0.000474

ClinVar

Significance: Benign

Submissions summary: Benign:2

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

Aug 10, 2023

- -

NDUFA13-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jul 12, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.71

BayesDel_addAF

Benign

0.0011

BayesDel_noAF

Uncertain

0.090

CADD

Pathogenic

DANN

Benign

0.96

DEOGEN2

Uncertain

0.74

D;T;.;.

Eigen

Pathogenic

0.84

Eigen_PC

Pathogenic

0.77

FATHMM_MKL

Benign

0.62

LIST_S2

Uncertain

0.92

D;D;D;D

M_CAP

Uncertain

0.25

MetaRNN

Benign

0.014

T;T;T;T

MetaSVM

Uncertain

0.19

MutationAssessor

Pathogenic

3.7

H;.;.;.

PROVEAN

Pathogenic

-5.0

D;.;.;N

REVEL

Pathogenic

0.79

Sift

Uncertain

0.0010

D;.;.;D

Sift4G

Uncertain

0.0020

D;D;D;D

Polyphen

1.0

D;.;.;.

Vest4

0.70

MVP

1.0

MPC

0.59

ClinPred

0.19

GERP RS

5.3

Varity_R

0.91

gMVP

0.83

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