rs3776141

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0850
Variant links:
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]

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ACMG classification

Classification made for transcript

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
NDUFS6NM_004553.6 linkuse as main transcriptc.187-4740G>A intron_variant ENST00000274137.10

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
NDUFS6ENST00000274137.10 linkuse as main transcriptc.187-4740G>A intron_variant 1 NM_004553.6 P1
NDUFS6ENST00000469176.1 linkuse as main transcriptc.187-4740G>A intron_variant 2

Frequencies

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs3776141; hg19: chr5-1809713; API