rs886060511

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6BP7

The NM_004553.6(NDUFS6):c.24C>T(p.Cys8Cys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000112 in 1,604,892 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 35)

Exomes 𝑓: 0.0000096 ( 0 hom. )

Consequence

NDUFS6
NM_004553.6 synonymous

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:1

Conservation

PhyloP100: -0.362

Publications

0 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: Likely_benign. The variant received -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.93).

BP6

Variant 5-1801441-C-T is Benign according to our data. Variant chr5-1801441-C-T is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 353189.

BP7

Synonymous conserved (PhyloP=-0.362 with no splicing effect.

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.24C>T	p.Cys8Cys	synonymous	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.24C>T	p.Cys8Cys	synonymous	Exon 1 of 4	ENSP00000274137.6	O75380
NDUFS6	ENST00000933864.1		c.24C>T	p.Cys8Cys	synonymous	Exon 1 of 4	ENSP00000603923.1
NDUFS6	ENST00000469176.1	TSL:2	c.24C>T	p.Cys8Cys	synonymous	Exon 1 of 3	ENSP00000422557.1	D6RBT3

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152260

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:

0.0000588

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000441

AC:

AN:

226898

AF XY:

0.00000794

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:

0.00000994

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000964

AC:

AN:

1452632

Hom.:

Cov.:

AF XY:

0.0000125

AC XY:

AN XY:

722642

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33378

American (AMR)

AF:

0.00

AC:

AN:

44572

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26042

East Asian (EAS)

AF:

0.00

AC:

AN:

39590

South Asian (SAS)

AF:

0.00

AC:

AN:

85998

European-Finnish (FIN)

AF:

0.00

AC:

AN:

46818

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5700

European-Non Finnish (NFE)

AF:

0.0000117

AC:

AN:

1110484

Other (OTH)

AF:

0.0000167

AC:

AN:

60050

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

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:

0.0000263

AC:

AN:

152260

Hom.:

Cov.:

AF XY:

0.0000403

AC XY:

AN XY:

74392

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41470

American (AMR)

AF:

0.00

AC:

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5202

South Asian (SAS)

AF:

0.00

AC:

AN:

4838

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10628

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000588

AC:

AN:

68048

Other (OTH)

AF:

0.00

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.0000299

Hom.:

Bravo

AF:

0.0000151

ClinVar

ClinVar submissions

Significance:Conflicting classifications of pathogenicity

Revision:criteria provided, conflicting classifications

View on ClinVar

Pathogenic

VUS

Benign

Condition

Mitochondrial complex I deficiency, nuclear type 1 (1)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

8.2

(source)

DANN

Benign

0.82

PhyloP100

-0.36

PromoterAI

0.032

Neutral

(source)

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

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over