19-1383644-A-T

Variant names:

• chr19-1383644-A-T
• rs114400263
• ENST00000546283.5:c.-220+36A>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The ENST00000546283.5(NDUFS7):​c.-220+36A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000226 in 1,330,022 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000023 (0 hom.)
• Consequence: NDUFS7 ENST00000546283.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.64

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]

TRF-GAA1-6 (HGNC:34873):

TRN-GTT2-6 (HGNC:34758):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.44).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRF-GAA1-6	unassigned_transcript_3181	c.-210T>A		upstream_gene_variant
TRN-GTT2-6	unassigned_transcript_3182	c.*8A>T		downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NDUFS7	ENST00000546283.5	c.-220+36A>T		intron_variant	Intron 1 of 7	2		ENSP00000440348.1
NDUFS7	ENST00000543289.5	n.-246A>T		upstream_gene_variant		2
NDUFS7	ENST00000545446.5	n.-231A>T		upstream_gene_variant		2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000226 AC: 3 AN: 1330022 Hom.: 0 Cov.: 29 AF XY: 0.00000305 AC XY: 2 AN XY: 655716

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000286

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.44
CADD	Benign	0.050
DANN	Benign	0.35
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: rs114400263; hg19: chr19-1383643;