rs3776141

Variant names:

• chr5-1809599-G-A
• rs3776141
• NM_004553.6:c.187-4740G>A

Your query was ambiguous. Multiple possible variants found:

• chr5-1809599-G-A
• chr5-1809599-G-C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 publications found

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]

NDUFS6 Gene-Disease associations (from GenCC):

• mitochondrial disease

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• mitochondrial complex I deficiency, nuclear type 9

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• mitochondrial complex I deficiency, nuclear type

  Inheritance: AR Classification: MODERATE Submitted by: Illumina
• mitochondrial complex I deficiency

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004553.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NDUFS6	NM_004553.6	MANE Select	c.187-4740G>A		intron	N/A	NP_004544.1	Q6IBC4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NDUFS6	ENST00000274137.10	TSL:1 MANE Select	c.187-4740G>A		intron	N/A	ENSP00000274137.6	O75380
	NDUFS6	ENST00000933864.1		c.487-4740G>A		intron	N/A	ENSP00000603923.1
	NDUFS6	ENST00000469176.1	TSL:2	c.187-4740G>A		intron	N/A	ENSP00000422557.1	D6RBT3

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

African (AFR) AF: 0.431 AC: 17876 AN: 41502

American (AMR) AF: 0.843 AC: 12887 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.848 AC: 2943 AN: 3470

East Asian (EAS) AF: 0.455 AC: 2346 AN: 5160

South Asian (SAS) AF: 0.728 AC: 3510 AN: 4822

European-Finnish (FIN) AF: 0.904 AC: 9593 AN: 10608

Middle Eastern (MID) AF: 0.786 AC: 231 AN: 294

European-Non Finnish (NFE) AF: 0.882 AC: 60002 AN: 68012

Other (OTH) AF: 0.777 AC: 1640 AN: 2110

Alfa AF: 0.795 Hom.: 6549

Bravo AF: 0.716

Asia WGS AF: 0.604 AC: 2101 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	3.4
DANN	Benign	0.81
PhyloP100		0.085
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3776141; hg19: chr5-1809713;