Variant chr19-19516240-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 8P and 4B. PVS1BS2

The NM_015965.7(NDUFA13):c.2T>C(p.Met1?) variant causes a start lost change. The variant allele was found at a frequency of 0.00000889 in 1,461,774 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000089 ( 0 hom. )

Consequence

NDUFA13
NM_015965.7 start_lost

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.40

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PVS1

Start lost variant, no new inframe start found.

BS2

High AC in GnomAdExome4 at 13 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NDUFA13	NM_015965.7 linkuse as main transcript	c.2T>C	p.Met1?	start_lost	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.2T>C	p.Met1?	start_lost	1/5	1	NM_015965.7	ENSP00000423673.1		Q9P0J0-1
ENSG00000258674	ENST00000555938.1 linkuse as main transcript	c.2T>C	p.Met1?	start_lost	1/7	2		ENSP00000452549.1		E7ENQ6

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251160

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135900

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:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000881

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000889

AC:

AN:

1461774

Hom.:

Cov.:

AF XY:

0.00000825

AC XY:

AN XY:

727186

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.0000188

Gnomad4 NFE exome

AF:

0.00000899

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Mitochondrial complex 1 deficiency, nuclear type 28

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Revvity Omics, Revvity

Sep 02, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Pathogenic

0.40

BayesDel_noAF

Pathogenic

0.34

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.27

T;T;.;.

Eigen

Uncertain

0.52

Eigen_PC

Uncertain

0.47

FATHMM_MKL

Benign

0.59

LIST_S2

Uncertain

0.90

D;D;D;D

M_CAP

Pathogenic

0.71

MetaRNN

Pathogenic

0.99

D;D;D;D

MetaSVM

Uncertain

0.63

PROVEAN

Uncertain

-2.8

D;.;.;N

REVEL

Pathogenic

0.72

Sift

Pathogenic

0.0

D;.;.;D

Sift4G

Pathogenic

0.0

D;D;D;D

Polyphen

1.0

D;.;.;.

Vest4

0.94

MutPred

0.99

Gain of glycosylation at M1 (P = 0.0273);Gain of glycosylation at M1 (P = 0.0273);Gain of glycosylation at M1 (P = 0.0273);Gain of glycosylation at M1 (P = 0.0273);

MVP

0.99

ClinPred

1.0

GERP RS

5.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.7

Varity_R

0.87

gMVP

0.73

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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