rs1018120

Positions:

• chr5-1806513-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004553.6(NDUFS6):​c.186+4139C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.494 in 152,176 control chromosomes in the GnomAD database, including 21,776 homozygotes. 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: 𝑓 0.49 (21776 hom., cov: 34)
• Consequence: NDUFS6 NM_004553.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.997

Genes affected

NDUFS6 (HGNC:7713): (NADH:ubiquinone oxidoreductase subunit S6) This gene encodes a subunit of the NADH:ubiquinone oxidoreductase (complex I), which is the first enzyme complex in the electron transport chain of mitochondria. This complex functions in the transfer of electrons from NADH to the respiratory chain. The subunit encoded by this gene is one of seven subunits in the iron-sulfur protein fraction. Mutations in this gene cause mitochondrial complex I deficiency, a disease that causes a wide variety of clinical disorders, including neonatal disease and adult-onset neurodegenerative disorders.[provided by RefSeq, Oct 2009]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.641 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NDUFS6	NM_004553.6	c.186+4139C>T		intron_variant		ENST00000274137.10	NP_004544.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NDUFS6	ENST00000274137.10	c.186+4139C>T		intron_variant		1	NM_004553.6	ENSP00000274137	P1
NDUFS6	ENST00000469176.1	c.186+4139C>T		intron_variant		2		ENSP00000422557

Frequencies

GnomAD3 genomes AF: 0.494 AC: 75124 AN: 152058 Hom.: 21788 Cov.: 34

Gnomad AFR AF: 0.182

Gnomad AMI AF: 0.571

Gnomad AMR AF: 0.554

Gnomad ASJ AF: 0.695

Gnomad EAS AF: 0.281

Gnomad SAS AF: 0.506

Gnomad FIN AF: 0.654

Gnomad MID AF: 0.665

Gnomad NFE AF: 0.646

Gnomad OTH AF: 0.569

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.494 AC: 75113 AN: 152176 Hom.: 21776 Cov.: 34 AF XY: 0.494 AC XY: 36757 AN XY: 74414

Gnomad4 AFR AF: 0.182

Gnomad4 AMR AF: 0.553

Gnomad4 ASJ AF: 0.695

Gnomad4 EAS AF: 0.280

Gnomad4 SAS AF: 0.506

Gnomad4 FIN AF: 0.654

Gnomad4 NFE AF: 0.646

Gnomad4 OTH AF: 0.566

Alfa AF: 0.600 Hom.: 12349

Bravo AF: 0.473

Asia WGS AF: 0.390 AC: 1357 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.33
DANN	Benign	0.64
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: rs1018120; hg19: chr5-1806627; COSMIC: COSV56876707; COSMIC: COSV56876707;