19-1384022-G-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_024407.5(NDUFS7):c.16+80G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0166 in 1,462,992 control chromosomes in the GnomAD database, including 285 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.013 (22 hom., cov: 33)
  • Exomes 𝑓: 0.017 (263 hom.)
• Consequence: NDUFS7 NM_024407.5 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.592

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BP6: Variant 19-1384022-G-C is Benign according to our data. Variant chr19-1384022-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 1218579.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0127 (1929/152354) while in subpopulation SAS AF= 0.0259 (125/4832). AF 95% confidence interval is 0.0222. There are 22 homozygotes in gnomad4. There are 914 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 22 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NDUFS7	NM_024407.5	c.16+80G>C		intron_variant		ENST00000233627.14
NDUFS7	NM_001363602.2	c.16+80G>C		intron_variant
NDUFS7	XM_017026768.3	c.16+80G>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NDUFS7	ENST00000233627.14	c.16+80G>C		intron_variant		1	NM_024407.5	P1

Frequencies

GnomAD3 genomes AF: 0.0127 AC: 1930 AN: 152240 Hom.: 22 Cov.: 33

Gnomad AFR AF: 0.00330

Gnomad AMI AF: 0.0352

Gnomad AMR AF: 0.0181

Gnomad ASJ AF: 0.00662

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.0256

Gnomad FIN AF: 0.00508

Gnomad MID AF: 0.0223

Gnomad NFE AF: 0.0181

Gnomad OTH AF: 0.0191

GnomAD4 exome AF: 0.0171 AC: 22422 AN: 1310638 Hom.: 263 Cov.: 22 AF XY: 0.0174 AC XY: 11269 AN XY: 647354

Gnomad4 AFR exome AF: 0.00344

Gnomad4 AMR exome AF: 0.0115

Gnomad4 ASJ exome AF: 0.00952

Gnomad4 EAS exome AF: 0.0000913

Gnomad4 SAS exome AF: 0.0256

Gnomad4 FIN exome AF: 0.00676

Gnomad4 NFE exome AF: 0.0182

Gnomad4 OTH exome AF: 0.0163

GnomAD4 genome AF: 0.0127 AC: 1929 AN: 152354 Hom.: 22 Cov.: 33 AF XY: 0.0123 AC XY: 914 AN XY: 74506

Gnomad4 AFR AF: 0.00327

Gnomad4 AMR AF: 0.0181

Gnomad4 ASJ AF: 0.00662

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.0259

Gnomad4 FIN AF: 0.00508

Gnomad4 NFE AF: 0.0181

Gnomad4 OTH AF: 0.0189

Alfa AF: 0.0146 Hom.: 2

Bravo AF: 0.0122

Asia WGS AF: 0.00635 AC: 23 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 23, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
Cadd	Benign	2.7
Dann	Benign	0.69
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

Other links and lift over

dbSNP: rs113443464; hg19: chr19-1384021;