1-161213726-C-T

Position:

chr1-161213726-C-T

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_001377299.1(NDUFS2):c.1290C>T(p.Ala430Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.138 in 1,613,872 control chromosomes in the GnomAD database, including 17,249 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.12 ( 1468 hom., cov: 32)

Exomes 𝑓: 0.14 ( 15781 hom. )

Consequence

NDUFS2
NM_001377299.1 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: -0.570

Variant links:

Genes affected

NDUFS2 (HGNC:7708): (NADH:ubiquinone oxidoreductase core subunit S2) The protein encoded by this gene is a core subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (complex I). Mammalian mitochondrial complex I is composed of at least 43 different subunits, 7 of which are encoded by the mitochondrial genome, and the rest are the products of nuclear genes. The iron-sulfur protein fraction of complex I is made up of 7 subunits, including this gene product. Complex I catalyzes the NADH oxidation with concomitant ubiquinone reduction and proton ejection out of the mitochondria. Mutations in this gene are associated with mitochondrial complex I deficiency. Alternatively spliced transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Oct 2009]

NDUFS2 links:

NDUFS2 (HGNC:):

NDUFS2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.25).

BP6

Variant 1-161213726-C-T is Benign according to our data. Variant chr1-161213726-C-T is described in ClinVar as [Benign]. Clinvar id is 129698.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-161213726-C-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-0.57 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.317 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NDUFS2	NM_001377299.1 linkuse as main transcript	c.1290C>T	p.Ala430Ala	synonymous_variant	12/14	ENST00000676972.1	NP_001364228.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NDUFS2	ENST00000676972.1 linkuse as main transcript	c.1290C>T	p.Ala430Ala	synonymous_variant	12/14		NM_001377299.1	ENSP00000503117.1		O75306-1

Frequencies

GnomAD3 genomes

AF:

0.123

AC:

18768

AN:

152028

Hom.:

1472

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0477

Gnomad AMI

AF:

0.136

Gnomad AMR

AF:

0.203

Gnomad ASJ

AF:

0.175

Gnomad EAS

AF:

0.330

Gnomad SAS

AF:

0.0982

Gnomad FIN

AF:

0.114

Gnomad MID

AF:

0.174

Gnomad NFE

AF:

0.136

Gnomad OTH

AF:

0.129

GnomAD3 exomes

AF:

0.158

AC:

39670

AN:

251470

Hom.:

3949

AF XY:

0.152

AC XY:

20713

AN XY:

135904

show subpopulations

Gnomad AFR exome

AF:

0.0453

Gnomad AMR exome

AF:

0.255

Gnomad ASJ exome

AF:

0.186

Gnomad EAS exome

AF:

0.333

Gnomad SAS exome

AF:

0.104

Gnomad FIN exome

AF:

0.108

Gnomad NFE exome

AF:

0.137

Gnomad OTH exome

AF:

0.170

GnomAD4 exome

AF:

0.139

AC:

203756

AN:

1461726

Hom.:

15781

Cov.:

AF XY:

0.139

AC XY:

100810

AN XY:

727168

show subpopulations

Gnomad4 AFR exome

AF:

0.0401

Gnomad4 AMR exome

AF:

0.248

Gnomad4 ASJ exome

AF:

0.186

Gnomad4 EAS exome

AF:

0.325

Gnomad4 SAS exome

AF:

0.103

Gnomad4 FIN exome

AF:

0.109

Gnomad4 NFE exome

AF:

0.134

Gnomad4 OTH exome

AF:

0.145

GnomAD4 genome

AF:

0.123

AC:

18764

AN:

152146

Hom.:

1468

Cov.:

AF XY:

0.125

AC XY:

9271

AN XY:

74372

show subpopulations

Gnomad4 AFR

AF:

0.0478

Gnomad4 AMR

AF:

0.203

Gnomad4 ASJ

AF:

0.175

Gnomad4 EAS

AF:

0.330

Gnomad4 SAS

AF:

0.0968

Gnomad4 FIN

AF:

0.114

Gnomad4 NFE

AF:

0.136

Gnomad4 OTH

AF:

0.129

Alfa

AF:

0.142

Hom.:

2296

Bravo

AF:

0.130

Asia WGS

AF:

0.204

AC:

708

AN:

3478

EpiCase

AF:

0.141

EpiControl

AF:

0.146

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:4

Benign, no assertion criteria provided	clinical testing	Mayo Clinic Laboratories, Mayo Clinic	Feb 22, 2016	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

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 1 deficiency, nuclear type 6

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Apr 11, 2023

- -

Mitochondrial complex I deficiency, nuclear type 1

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.25

CADD

Benign

7.9

DANN

Benign

0.80

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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