5-1801318-A-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The ENST00000887752.1(MRPL36):c.-972T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.846 in 1,497,886 control chromosomes in the GnomAD database, including 547,640 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.74 ( 45242 hom., cov: 37)

Exomes 𝑓: 0.86 ( 502398 hom. )

Consequence

MRPL36
ENST00000887752.1 5_prime_UTR

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.904

Publications

6 publications found

Variant links:

Genes affected

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:

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

NDUFS6 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-1.01).

BP6

Variant 5-1801318-A-G is Benign according to our data. Variant chr5-1801318-A-G is described in ClinVar as Benign. ClinVar VariationId is 1253294.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.89 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000887752.1. 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.-100A>G		upstream_gene	N/A	NP_004544.1	Q6IBC4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
MRPL36	ENST00000887752.1		c.-972T>C	5_prime_UTR	Exon 1 of 2	ENSP00000557811.1
MRPL36	ENST00000887753.1		c.-93T>C	5_prime_UTR	Exon 1 of 2	ENSP00000557812.1
MRPL36	ENST00000505818.1	TSL:3	c.-13+16T>C	intron	N/A	ENSP00000427152.1	Q9P0J6

Frequencies

GnomAD3 genomes

AF:

0.744

AC:

112810

AN:

151598

Hom.:

45235

Cov.:

show subpopulations

Gnomad AFR

AF:

0.437

Gnomad AMI

AF:

0.945

Gnomad AMR

AF:

0.844

Gnomad ASJ

AF:

0.848

Gnomad EAS

AF:

0.451

Gnomad SAS

AF:

0.729

Gnomad FIN

AF:

0.918

Gnomad MID

AF:

0.794

Gnomad NFE

AF:

0.895

Gnomad OTH

AF:

0.783

GnomAD4 exome

AF:

0.857

AC:

1154278

AN:

1346170

Hom.:

502398

Cov.:

AF XY:

0.856

AC XY:

563178

AN XY:

658300

show subpopulations

African (AFR)

AF:

0.420

AC:

12996

AN:

30958

American (AMR)

AF:

0.863

AC:

27811

AN:

32238

Ashkenazi Jewish (ASJ)

AF:

0.846

AC:

19269

AN:

22790

East Asian (EAS)

AF:

0.484

AC:

17691

AN:

36552

South Asian (SAS)

AF:

0.741

AC:

55072

AN:

74360

European-Finnish (FIN)

AF:

0.914

AC:

31047

AN:

33954

Middle Eastern (MID)

AF:

0.838

AC:

4422

AN:

5276

European-Non Finnish (NFE)

AF:

0.892

AC:

940083

AN:

1054034

Other (OTH)

AF:

0.819

AC:

45887

AN:

56008

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

7672

15345

23017

30690

38362

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

20808

41616

62424

83232

104040

<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:

0.744

AC:

112843

AN:

151716

Hom.:

45242

Cov.:

AF XY:

0.744

AC XY:

55177

AN XY:

74150

show subpopulations

African (AFR)

AF:

0.437

AC:

18068

AN:

41386

American (AMR)

AF:

0.844

AC:

12890

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.848

AC:

2931

AN:

3458

East Asian (EAS)

AF:

0.450

AC:

2319

AN:

5150

South Asian (SAS)

AF:

0.730

AC:

3519

AN:

4820

European-Finnish (FIN)

AF:

0.918

AC:

9697

AN:

10558

Middle Eastern (MID)

AF:

0.789

AC:

232

AN:

294

European-Non Finnish (NFE)

AF:

0.895

AC:

60688

AN:

67772

Other (OTH)

AF:

0.781

AC:

1647

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

1185

2371

3556

4742

5927

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

812

1624

2436

3248

4060

<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:

0.663

Hom.:

7876

Bravo

AF:

0.724

Asia WGS

AF:

0.602

AC:

2095

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

2.3

(source)

DANN

Benign

0.29

PhyloP100

-0.90

PromoterAI

-0.061

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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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