rs1142530

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_024407.5(NDUFS7):c.68C>T(p.Pro23Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.592 in 1,610,648 control chromosomes in the GnomAD database, including 287,790 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.52 ( 21647 hom., cov: 33)

Exomes 𝑓: 0.60 ( 266143 hom. )

Consequence

NDUFS7
NM_024407.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: -0.979

Variant links:

Genes affected

NDUFS7 (HGNC:7714): (NADH:ubiquinone oxidoreductase core subunit S7) This gene encodes a protein that is a subunit of one of the complexes that forms the mitochondrial respiratory chain. This protein is one of over 40 subunits found in complex I, the nicotinamide adenine dinucleotide (NADH):ubiquinone oxidoreductase. This complex functions in the transfer of electrons from NADH to the respiratory chain, and ubiquinone is believed to be the immediate electron acceptor for the enzyme. Mutations in this gene cause Leigh syndrome due to mitochondrial complex I deficiency, a severe neurological disorder that results in bilaterally symmetrical necrotic lesions in subcortical brain regions. [provided by RefSeq, Jul 2008]

NDUFS7 links:

(HGNC:):

links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=1.1169489E-5).

BP6

Variant 19-1388539-C-T is Benign according to our data. Variant chr19-1388539-C-T is described in ClinVar as [Benign]. Clinvar id is 129702.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-1388539-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.619 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
NDUFS7	NM_024407.5 linkuse as main transcript	c.68C>T	p.Pro23Leu	missense_variant	3/8	ENST00000233627.14
NDUFS7	NM_001363602.2 linkuse as main transcript	c.68C>T	p.Pro23Leu	missense_variant	3/8
NDUFS7	XM_017026768.3 linkuse as main transcript	c.68C>T	p.Pro23Leu	missense_variant	3/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NDUFS7	ENST00000233627.14 linkuse as main transcript	c.68C>T	p.Pro23Leu	missense_variant	3/8	1	NM_024407.5	P1	O75251-1
	ENST00000626781.2 linkuse as main transcript	n.938+189G>A		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes

AF:

0.522

AC:

79346

AN:

151926

Hom.:

21646

Cov.:

show subpopulations

Gnomad AFR

AF:

0.373

Gnomad AMI

AF:

0.771

Gnomad AMR

AF:

0.488

Gnomad ASJ

AF:

0.601

Gnomad EAS

AF:

0.322

Gnomad SAS

AF:

0.553

Gnomad FIN

AF:

0.526

Gnomad MID

AF:

0.665

Gnomad NFE

AF:

0.624

Gnomad OTH

AF:

0.570

GnomAD3 exomes

AF:

0.546

AC:

134740

AN:

246744

Hom.:

37889

AF XY:

0.556

AC XY:

74749

AN XY:

134330

show subpopulations

Gnomad AFR exome

AF:

0.372

Gnomad AMR exome

AF:

0.499

Gnomad ASJ exome

AF:

0.606

Gnomad EAS exome

AF:

0.299

Gnomad SAS exome

AF:

0.579

Gnomad FIN exome

AF:

0.528

Gnomad NFE exome

AF:

0.614

Gnomad OTH exome

AF:

0.566

GnomAD4 exome

AF:

0.600

AC:

874836

AN:

1458606

Hom.:

266143

Cov.:

AF XY:

0.601

AC XY:

435964

AN XY:

725652

show subpopulations

Gnomad4 AFR exome

AF:

0.365

Gnomad4 AMR exome

AF:

0.497

Gnomad4 ASJ exome

AF:

0.604

Gnomad4 EAS exome

AF:

0.344

Gnomad4 SAS exome

AF:

0.580

Gnomad4 FIN exome

AF:

0.528

Gnomad4 NFE exome

AF:

0.625

Gnomad4 OTH exome

AF:

0.587

GnomAD4 genome

AF:

0.522

AC:

79373

AN:

152042

Hom.:

21647

Cov.:

AF XY:

0.513

AC XY:

38160

AN XY:

74316

show subpopulations

Gnomad4 AFR

AF:

0.373

Gnomad4 AMR

AF:

0.487

Gnomad4 ASJ

AF:

0.601

Gnomad4 EAS

AF:

0.321

Gnomad4 SAS

AF:

0.555

Gnomad4 FIN

AF:

0.526

Gnomad4 NFE

AF:

0.624

Gnomad4 OTH

AF:

0.568

Alfa

AF:

0.598

Hom.:

65675

Bravo

AF:

0.511

TwinsUK

AF:

0.628

AC:

2328

ALSPAC

AF:

0.631

AC:

2430

ESP6500AA

AF:

0.380

AC:

1674

ESP6500EA

AF:

0.623

AC:

5353

ExAC

AF:

0.543

AC:

65719

Asia WGS

AF:

0.411

AC:

1428

AN:

3478

EpiCase

AF:

0.621

EpiControl

AF:

0.627

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, no assertion criteria provided	clinical testing	Mayo Clinic Laboratories, Mayo Clinic	Feb 19, 2016	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Feb 01, 2024	- -

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	Jul 24, 2022	- -
Likely benign, no assertion criteria provided	clinical testing	Genetic Services Laboratory, University of Chicago	-	Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. -

Mitochondrial complex I deficiency, nuclear type 1

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Leigh syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

Mitochondrial complex 1 deficiency, nuclear type 3

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 14, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.068

BayesDel_addAF

Benign

-0.66

BayesDel_noAF

Benign

-0.58

Cadd

Benign

9.0

Dann

Benign

0.66

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.21

MetaRNN

Benign

0.000011

T;T;T;T;T;T;T

MetaSVM

Benign

-0.92

MutationAssessor

Benign

0.69

N;N;.;.;N;.;.

MutationTaster

Benign

1.0

P;P;P;P;P

PrimateAI

Benign

0.43

PROVEAN

Benign

0.96

N;N;.;N;N;.;N

REVEL

Benign

0.070

Sift

Benign

0.40

T;T;.;T;T;.;T

Sift4G

Benign

0.15

T;T;T;T;T;T;T

Polyphen

0.0, 0.0010

.;B;.;B;.;.;.

Vest4

0.12

MPC

0.53

ClinPred

0.0074

GERP RS

0.84

RBP_binding_hub_radar

1.1

RBP_regulation_power_radar

2.2

Varity_R

0.023

gMVP

0.44

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