rs2074897

Positions:

• chr19-1391236-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_024407.5(NDUFS7):​c.455+71G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.444 in 1,539,078 control chromosomes in the GnomAD database, including 158,271 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.35 (11075 hom., cov: 31)
  • Exomes 𝑓: 0.46 (147196 hom.)
• Consequence: NDUFS7 NM_024407.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.741

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 19-1391236-G-A is Benign according to our data. Variant chr19-1391236-G-A is described in ClinVar as [Benign]. Clinvar id is 1185398.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.47 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NDUFS7	NM_024407.5	c.455+71G>A		intron_variant		ENST00000233627.14	NP_077718.3
NDUFS7	NM_001363602.2	c.455+71G>A		intron_variant			NP_001350531.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NDUFS7	ENST00000233627.14	c.455+71G>A		intron_variant		1	NM_024407.5	ENSP00000233627.9

Frequencies

GnomAD3 genomes AF: 0.347 AC: 52740 AN: 151828 Hom.: 11078 Cov.: 31

Gnomad AFR AF: 0.101

Gnomad AMI AF: 0.658

Gnomad AMR AF: 0.367

Gnomad ASJ AF: 0.480

Gnomad EAS AF: 0.296

Gnomad SAS AF: 0.408

Gnomad FIN AF: 0.380

Gnomad MID AF: 0.528

Gnomad NFE AF: 0.475

Gnomad OTH AF: 0.388

GnomAD4 exome AF: 0.455 AC: 631212 AN: 1387130 Hom.: 147196 AF XY: 0.456 AC XY: 313328 AN XY: 687570

Gnomad4 AFR exome AF: 0.0871

Gnomad4 AMR exome AF: 0.390

Gnomad4 ASJ exome AF: 0.477

Gnomad4 EAS exome AF: 0.316

Gnomad4 SAS exome AF: 0.431

Gnomad4 FIN exome AF: 0.383

Gnomad4 NFE exome AF: 0.479

Gnomad4 OTH exome AF: 0.438

GnomAD4 genome AF: 0.347 AC: 52730 AN: 151948 Hom.: 11075 Cov.: 31 AF XY: 0.343 AC XY: 25470 AN XY: 74242

Gnomad4 AFR AF: 0.100

Gnomad4 AMR AF: 0.367

Gnomad4 ASJ AF: 0.480

Gnomad4 EAS AF: 0.296

Gnomad4 SAS AF: 0.410

Gnomad4 FIN AF: 0.380

Gnomad4 NFE AF: 0.475

Gnomad4 OTH AF: 0.382

Alfa AF: 0.395 Hom.: 2141

Bravo AF: 0.337

Asia WGS AF: 0.306 AC: 1063 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

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 23, 2018	- -

Mitochondrial complex 1 deficiency, nuclear type 3 Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 14, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	4.7
DANN	Benign	0.78
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs2074897; hg19: chr19-1391235; COSMIC: COSV52040979; COSMIC: COSV52040979;