rs1127566

Positions:

Variant summary

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

The NM_005006.7(NDUFS1):c.966G>T(p.Ala322Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.441 in 1,609,870 control chromosomes in the GnomAD database, including 161,075 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.50 ( 19892 hom., cov: 33)

Exomes 𝑓: 0.43 ( 141183 hom. )

Consequence

NDUFS1
NM_005006.7 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: -1.04

Variant links:

Genes affected

NDUFS1 (HGNC:7707): (NADH:ubiquinone oxidoreductase core subunit S1) The protein encoded by this gene belongs to the complex I 75 kDa subunit family. Mammalian complex I is composed of 45 different subunits. It locates at the mitochondrial inner membrane. This protein has NADH dehydrogenase activity and oxidoreductase activity. It transfers electrons from NADH to the respiratory chain. The immediate electron acceptor for the enzyme is believed to be ubiquinone. This protein is the largest subunit of complex I and it is a component of the iron-sulfur (IP) fragment of the enzyme. It may form part of the active site crevice where NADH is oxidized. Mutations in this gene are associated with complex I deficiency. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2011]

NDUFS1 links:

NDUFS1 (HGNC:):

NDUFS1 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=-0.26).

BP6

Variant 2-206144039-C-A is Benign according to our data. Variant chr2-206144039-C-A is described in ClinVar as [Benign]. Clinvar id is 129696.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-206144039-C-A is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-1.04 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.636 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NDUFS1	NM_005006.7 linkuse as main transcript	c.966G>T	p.Ala322Ala	synonymous_variant	10/19	ENST00000233190.11	NP_004997.4	P28331-1E5KRK5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NDUFS1	ENST00000233190.11 linkuse as main transcript	c.966G>T	p.Ala322Ala	synonymous_variant	10/19	1	NM_005006.7	ENSP00000233190.5		P28331-1

Frequencies

GnomAD3 genomes

AF:

0.501

AC:

76053

AN:

151952

Hom.:

19856

Cov.:

show subpopulations

Gnomad AFR

AF:

0.642

Gnomad AMI

AF:

0.282

Gnomad AMR

AF:

0.526

Gnomad ASJ

AF:

0.546

Gnomad EAS

AF:

0.280

Gnomad SAS

AF:

0.339

Gnomad FIN

AF:

0.520

Gnomad MID

AF:

0.513

Gnomad NFE

AF:

0.434

Gnomad OTH

AF:

0.512

GnomAD3 exomes

AF:

0.454

AC:

114194

AN:

251364

Hom.:

27017

AF XY:

0.445

AC XY:

60407

AN XY:

135870

show subpopulations

Gnomad AFR exome

AF:

0.642

Gnomad AMR exome

AF:

0.520

Gnomad ASJ exome

AF:

0.536

Gnomad EAS exome

AF:

0.287

Gnomad SAS exome

AF:

0.344

Gnomad FIN exome

AF:

0.519

Gnomad NFE exome

AF:

0.444

Gnomad OTH exome

AF:

0.474

GnomAD4 exome

AF:

0.435

AC:

633692

AN:

1457800

Hom.:

141183

Cov.:

AF XY:

0.432

AC XY:

313373

AN XY:

725430

show subpopulations

Gnomad4 AFR exome

AF:

0.654

Gnomad4 AMR exome

AF:

0.522

Gnomad4 ASJ exome

AF:

0.537

Gnomad4 EAS exome

AF:

0.268

Gnomad4 SAS exome

AF:

0.349

Gnomad4 FIN exome

AF:

0.516

Gnomad4 NFE exome

AF:

0.430

Gnomad4 OTH exome

AF:

0.452

GnomAD4 genome

AF:

0.501

AC:

76139

AN:

152070

Hom.:

19892

Cov.:

AF XY:

0.500

AC XY:

37118

AN XY:

74300

show subpopulations

Gnomad4 AFR

AF:

0.642

Gnomad4 AMR

AF:

0.526

Gnomad4 ASJ

AF:

0.546

Gnomad4 EAS

AF:

0.280

Gnomad4 SAS

AF:

0.340

Gnomad4 FIN

AF:

0.520

Gnomad4 NFE

AF:

0.434

Gnomad4 OTH

AF:

0.508

Alfa

AF:

0.450

Hom.:

7744

Bravo

AF:

0.506

Asia WGS

AF:

0.318

AC:

1106

AN:

3478

EpiCase

AF:

0.451

EpiControl

AF:

0.462

ClinVar

Significance: Benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:4

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

not specified

Benign:2

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. -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

Leigh syndrome

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. -

Mitochondrial complex I deficiency, nuclear type 1

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

Mitochondrial complex 1 deficiency, nuclear type 5

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Sep 05, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.26

CADD

Benign

8.6

DANN

Benign

0.72

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.8

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