Variant chr19-1383650-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1

The ENST00000546283.5(NDUFS7):c.-220+42G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.461 in 1,488,834 control chromosomes in the GnomAD database, including 160,364 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.42 ( 13486 hom., cov: 33)

Exomes 𝑓: 0.47 ( 146878 hom. )

Consequence

NDUFS7
ENST00000546283.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.322

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 -18 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.42).

BP6

Variant 19-1383650-G-T is Benign according to our data. Variant chr19-1383650-G-T is described in ClinVar as [Benign]. Clinvar id is 684335.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.473 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
	use as main transcript	n.1383650G>T		intergenic_region
TRN-GTT2-6	unassigned_transcript_3183 use as main transcript	c.*14G>T		downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NDUFS7	ENST00000546283.5 linkuse as main transcript	c.-220+42G>T		intron_variant		2		ENSP00000440348.1		O75251-2

Frequencies

GnomAD3 genomes

AF:

0.416

AC:

63323

AN:

152082

Hom.:

13483

Cov.:

show subpopulations

Gnomad AFR

AF:

0.332

Gnomad AMI

AF:

0.657

Gnomad AMR

AF:

0.397

Gnomad ASJ

AF:

0.481

Gnomad EAS

AF:

0.306

Gnomad SAS

AF:

0.416

Gnomad FIN

AF:

0.382

Gnomad MID

AF:

0.544

Gnomad NFE

AF:

0.478

Gnomad OTH

AF:

0.448

GnomAD4 exome

AF:

0.466

AC:

623182

AN:

1336634

Hom.:

146878

Cov.:

AF XY:

0.466

AC XY:

306982

AN XY:

659092

show subpopulations

Gnomad4 AFR exome

AF:

0.326

Gnomad4 AMR exome

AF:

0.404

Gnomad4 ASJ exome

AF:

0.476

Gnomad4 EAS exome

AF:

0.324

Gnomad4 SAS exome

AF:

0.438

Gnomad4 FIN exome

AF:

0.383

Gnomad4 NFE exome

AF:

0.481

Gnomad4 OTH exome

AF:

0.456

GnomAD4 genome

AF:

0.416

AC:

63344

AN:

152200

Hom.:

13486

Cov.:

AF XY:

0.410

AC XY:

30498

AN XY:

74428

show subpopulations

Gnomad4 AFR

AF:

0.332

Gnomad4 AMR

AF:

0.396

Gnomad4 ASJ

AF:

0.481

Gnomad4 EAS

AF:

0.306

Gnomad4 SAS

AF:

0.418

Gnomad4 FIN

AF:

0.382

Gnomad4 NFE

AF:

0.478

Gnomad4 OTH

AF:

0.443

Alfa

AF:

0.456

Hom.:

14709

Bravo

AF:

0.414

Asia WGS

AF:

0.323

AC:

1123

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 14, 2018	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.42

CADD

Benign

1.6

DANN

Benign

0.79

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

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