5-1801442-C-G

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_004553.6(NDUFS6):c.25C>G(p.Arg9Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000312 in 1,605,048 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R9W) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 36)

Exomes 𝑓: 0.0000028 ( 0 hom. )

Consequence

NDUFS6
NM_004553.6 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.282

Publications

1 publications found

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]

NDUFS6 links:

MRPL36 (HGNC:14490): (mitochondrial ribosomal protein L36) Mammalian mitochondrial ribosomal proteins are encoded by nuclear genes and help in protein synthesis within the mitochondrion. Mitochondrial ribosomes (mitoribosomes) consist of a small 28S subunit and a large 39S subunit. They have an estimated 75% protein to rRNA composition compared to prokaryotic ribosomes, where this ratio is reversed. Another difference between mammalian mitoribosomes and prokaryotic ribosomes is that the latter contain a 5S rRNA. Among different species, the proteins comprising the mitoribosome differ greatly in sequence, and sometimes in biochemical properties, which prevents easy recognition by sequence homology. This gene encodes a 39S subunit protein. A pseudogene corresponding to this gene is found on chromosome 2p. [provided by RefSeq, Jul 2008]

MRPL36 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.13040996).

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.25C>G	p.Arg9Gly	missense	Exon 1 of 4	NP_004544.1	Q6IBC4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NDUFS6	ENST00000274137.10	TSL:1 MANE Select	c.25C>G	p.Arg9Gly	missense	Exon 1 of 4	ENSP00000274137.6	O75380
NDUFS6	ENST00000933864.1		c.25C>G	p.Arg9Gly	missense	Exon 1 of 4	ENSP00000603923.1
NDUFS6	ENST00000469176.1	TSL:2	c.25C>G	p.Arg9Gly	missense	Exon 1 of 3	ENSP00000422557.1	D6RBT3

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152266

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000132

AC:

AN:

227020

AF XY:

0.00000793

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000298

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000275

AC:

AN:

1452782

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

722726

show subpopulations

African (AFR)

AF:

0.0000300

AC:

AN:

33376

American (AMR)

AF:

0.00

AC:

AN:

44572

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26040

East Asian (EAS)

AF:

0.00

AC:

AN:

39586

South Asian (SAS)

AF:

0.00

AC:

AN:

86024

European-Finnish (FIN)

AF:

0.00

AC:

AN:

46890

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5716

European-Non Finnish (NFE)

AF:

0.00000270

AC:

AN:

1110520

Other (OTH)

AF:

0.00

AC:

AN:

60058

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152266

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74394

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41474

American (AMR)

AF:

0.00

AC:

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5206

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68050

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0000191

Hom.:

Bravo

AF:

0.00000378

ExAC

AF:

0.0000168

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.087

BayesDel_noAF

Benign

-0.34

CADD

Benign

(source)

DANN

Benign

0.61

DEOGEN2

Benign

0.060

Eigen

Benign

-0.92

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.012

LIST_S2

Benign

0.74

M_CAP

Benign

0.032

MetaRNN

Benign

0.13

MetaSVM

Benign

-0.71

MutationAssessor

Benign

2.0

PhyloP100

0.28

PrimateAI

Uncertain

0.77

PROVEAN

Benign

-1.3

REVEL

Benign

0.16

Sift

Uncertain

0.021

Sift4G

Benign

0.23

Polyphen

0.019

Vest4

0.35

MutPred

0.42

Loss of MoRF binding (P = 6e-04)

MVP

0.57

MPC

0.18

ClinPred

0.11

GERP RS

0.039

PromoterAI

-0.026

Neutral

(source)

Varity_R

0.20

gMVP

0.76

Mutation Taster

=100/0

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over