2-206123849-C-A

Variant summary

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

The NM_005006.7(NDUFS1):c.*336G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.493 in 205,206 control chromosomes in the GnomAD database, including 27,059 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.52 ( 21981 hom., cov: 32)

Exomes 𝑓: 0.42 ( 5078 hom. )

Consequence

NDUFS1
NM_005006.7 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.0460

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:

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 (BayesDel_noAF=-0.89).

BP6

Variant 2-206123849-C-A is Benign according to our data. Variant chr2-206123849-C-A is described in ClinVar as [Benign]. Clinvar id is 333774.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.727 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NDUFS1	NM_005006.7 linkuse as main transcript	c.*336G>T		3_prime_UTR_variant	19/19	ENST00000233190.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NDUFS1	ENST00000233190.11 linkuse as main transcript	c.*336G>T		3_prime_UTR_variant	19/19	1	NM_005006.7	P1	P28331-1
NDUFS1	ENST00000423725.5 linkuse as main transcript	c.*336G>T		3_prime_UTR_variant	18/18	2			P28331-4

Frequencies

GnomAD3 genomes

AF:

0.517

AC:

78503

AN:

151750

Hom.:

21945

Cov.:

show subpopulations

Gnomad AFR

AF:

0.734

Gnomad AMI

AF:

0.260

Gnomad AMR

AF:

0.491

Gnomad ASJ

AF:

0.529

Gnomad EAS

AF:

0.248

Gnomad SAS

AF:

0.331

Gnomad FIN

AF:

0.518

Gnomad MID

AF:

0.506

Gnomad NFE

AF:

0.427

Gnomad OTH

AF:

0.527

GnomAD4 exome

AF:

0.422

AC:

22488

AN:

53336

Hom.:

5078

Cov.:

AF XY:

0.415

AC XY:

11492

AN XY:

27716

show subpopulations

Gnomad4 AFR exome

AF:

0.723

Gnomad4 AMR exome

AF:

0.450

Gnomad4 ASJ exome

AF:

0.521

Gnomad4 EAS exome

AF:

0.226

Gnomad4 SAS exome

AF:

0.303

Gnomad4 FIN exome

AF:

0.485

Gnomad4 NFE exome

AF:

0.421

Gnomad4 OTH exome

AF:

0.456

GnomAD4 genome

AF:

0.517

AC:

78592

AN:

151870

Hom.:

21981

Cov.:

AF XY:

0.515

AC XY:

38219

AN XY:

74202

show subpopulations

Gnomad4 AFR

AF:

0.734

Gnomad4 AMR

AF:

0.491

Gnomad4 ASJ

AF:

0.529

Gnomad4 EAS

AF:

0.248

Gnomad4 SAS

AF:

0.332

Gnomad4 FIN

AF:

0.518

Gnomad4 NFE

AF:

0.427

Gnomad4 OTH

AF:

0.523

Alfa

AF:

0.443

Hom.:

13677

Bravo

AF:

0.522

Asia WGS

AF:

0.304

AC:

1054

AN:

3468

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

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

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 13, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

Cadd

Benign

1.5

Dann

Benign

0.41

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.2

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