rs3776141

Positions:

• chr5-1809599-G-A
• chr5-1809599-G-C

Variant summary

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

The NM_004553.6(NDUFS6):​c.187-4740G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.735 in 152,186 control chromosomes in the GnomAD database, including 44,323 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 0.74 (44323 hom., cov: 34)
• Consequence: NDUFS6 NM_004553.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0850

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=-0.77).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.876 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NDUFS6	NM_004553.6	c.187-4740G>A		intron_variant		ENST00000274137.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NDUFS6	ENST00000274137.10	c.187-4740G>A		intron_variant		1	NM_004553.6	P1
NDUFS6	ENST00000469176.1	c.187-4740G>A		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.736 AC: 111854 AN: 152068 Hom.: 44314 Cov.: 34

Gnomad AFR AF: 0.431

Gnomad AMI AF: 0.944

Gnomad AMR AF: 0.842

Gnomad ASJ AF: 0.848

Gnomad EAS AF: 0.456

Gnomad SAS AF: 0.727

Gnomad FIN AF: 0.904

Gnomad MID AF: 0.791

Gnomad NFE AF: 0.882

Gnomad OTH AF: 0.779

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

GnomAD4 genome AF: 0.735 AC: 111889 AN: 152186 Hom.: 44323 Cov.: 34 AF XY: 0.736 AC XY: 54760 AN XY: 74418

Gnomad4 AFR AF: 0.431

Gnomad4 AMR AF: 0.843

Gnomad4 ASJ AF: 0.848

Gnomad4 EAS AF: 0.455

Gnomad4 SAS AF: 0.728

Gnomad4 FIN AF: 0.904

Gnomad4 NFE AF: 0.882

Gnomad4 OTH AF: 0.777

Alfa AF: 0.809 Hom.: 6477

Bravo AF: 0.716

Asia WGS AF: 0.604 AC: 2101 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	3.4
DANN	Benign	0.81
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: rs3776141; hg19: chr5-1809713;