19-1383551-G-C

Position:

• chr19-1383551-G-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The ENST00000546283.5(NDUFS7):​c.-277G>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0449 in 913,788 control chromosomes in the GnomAD database, including 1,091 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.036 (162 hom., cov: 33)
  • Exomes 𝑓: 0.047 (929 hom.)
• Consequence: NDUFS7 ENST00000546283.5 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -6.12

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.47).
• BP6: Variant 19-1383551-G-C is Benign according to our data. Variant chr19-1383551-G-C is described in ClinVar as [Benign]. Clinvar id is 672592.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0362 (5510/152354) while in subpopulation SAS AF= 0.0511 (247/4834). AF 95% confidence interval is 0.0466. There are 162 homozygotes in gnomad4. There are 2746 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 162 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
		n.1383551G>C		intergenic_region
TRN-GTT2-6	unassigned_transcript_3183	c.-12G>C		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NDUFS7	ENST00000546283.5	c.-277G>C		5_prime_UTR_variant	1/8	2		ENSP00000440348.1

Frequencies

GnomAD3 genomes AF: 0.0362 AC: 5509 AN: 152236 Hom.: 162 Cov.: 33

Gnomad AFR AF: 0.0111

Gnomad AMI AF: 0.00329

Gnomad AMR AF: 0.0285

Gnomad ASJ AF: 0.0499

Gnomad EAS AF: 0.000577

Gnomad SAS AF: 0.0511

Gnomad FIN AF: 0.0775

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.0480

Gnomad OTH AF: 0.0454

GnomAD4 exome AF: 0.0466 AC: 35478 AN: 761434 Hom.: 929 Cov.: 10 AF XY: 0.0469 AC XY: 18016 AN XY: 383762

Gnomad4 AFR exome AF: 0.00976

Gnomad4 AMR exome AF: 0.0262

Gnomad4 ASJ exome AF: 0.0475

Gnomad4 EAS exome AF: 0.000296

Gnomad4 SAS exome AF: 0.0492

Gnomad4 FIN exome AF: 0.0794

Gnomad4 NFE exome AF: 0.0481

Gnomad4 OTH exome AF: 0.0433

GnomAD4 genome AF: 0.0362 AC: 5510 AN: 152354 Hom.: 162 Cov.: 33 AF XY: 0.0369 AC XY: 2746 AN XY: 74506

Gnomad4 AFR AF: 0.0111

Gnomad4 AMR AF: 0.0285

Gnomad4 ASJ AF: 0.0499

Gnomad4 EAS AF: 0.000578

Gnomad4 SAS AF: 0.0511

Gnomad4 FIN AF: 0.0775

Gnomad4 NFE AF: 0.0480

Gnomad4 OTH AF: 0.0449

Alfa AF: 0.0170 Hom.: 14

Bravo AF: 0.0323

Asia WGS AF: 0.0180 AC: 65 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

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. -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.47
CADD	Benign	0.0010
DANN	Benign	0.42

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs117758624; hg19: chr19-1383550;