19-19516312-T-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_015965.7(NDUFA13):ā€‹c.74T>Gā€‹(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 (ā˜…).

Frequency

Genomes: š‘“ 0.00061 ( 2 hom., cov: 33)
Exomes š‘“: 0.00051 ( 5 hom. )

Consequence

NDUFA13
NM_015965.7 missense

Scores

6
7
5

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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 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.
BS1
Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.000606 (92/151916) while in subpopulation AMR AF= 0.00059 (9/15258). AF 95% confidence interval is 0.000307. There are 2 homozygotes in gnomad4. There are 52 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
High AC in GnomAd4 at 92 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
NDUFA13NM_015965.7 linkc.74T>G p.Leu25Trp missense_variant Exon 1 of 5 ENST00000507754.9 NP_057049.5 Q9P0J0-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
NDUFA13ENST00000507754.9 linkc.74T>G p.Leu25Trp missense_variant Exon 1 of 5 1 NM_015965.7 ENSP00000423673.1 Q9P0J0-1
ENSG00000258674ENST00000555938.1 linkc.74T>G p.Leu25Trp missense_variant Exon 1 of 7 2 ENSP00000452549.1 E7ENQ6

Frequencies

GnomAD3 genomes
AF:
0.000606
AC:
92
AN:
151916
Hom.:
2
Cov.:
33
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.:
0
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.:
5
Cov.:
32
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:
92
AN:
151916
Hom.:
2
Cov.:
33
AF XY:
0.000701
AC XY:
52
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.:
2
Bravo
AF:
0.000782
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.00163
AC:
14
ExAC
AF:
0.000634
AC:
77
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
Nov 07, 2024
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

NDUFA13-related disorder Benign:1
Jul 12, 2019
PreventionGenetics, part of Exact Sciences
Significance: Benign
Review Status: no assertion criteria provided
Collection Method: clinical testing

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
T
BayesDel_noAF
Uncertain
0.090
CADD
Pathogenic
31
DANN
Benign
0.96
DEOGEN2
Uncertain
0.74
D;T;.;.
Eigen
Pathogenic
0.84
Eigen_PC
Pathogenic
0.77
FATHMM_MKL
Benign
0.62
D
LIST_S2
Uncertain
0.92
D;D;D;D
M_CAP
Uncertain
0.25
D
MetaRNN
Benign
0.014
T;T;T;T
MetaSVM
Uncertain
0.19
D
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
T
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.

Other links and lift over

dbSNP: rs143629324; hg19: chr19-19627121; API