Genetic Variant MRPL36:c.-13+20_-13+21insC (chr5-1801313-C-CG) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_ModerateBA1

The ENST00000505818.1(MRPL36):c.-13+20_-13+21insC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.845 in 1,479,734 control chromosomes in the GnomAD database, including 540,383 homozygotes. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.74 ( 45200 hom., cov: 0)

Exomes 𝑓: 0.86 ( 495183 hom. )

Consequence

MRPL36
ENST00000505818.1 intron

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0150

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP6

Variant 5-1801313-C-CG is Benign according to our data. Variant chr5-1801313-C-CG is described in ClinVar as [Benign]. Clinvar id is 1266183.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.889 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
MRPL36	XM_011514080.3 link	c.33+20_33+21insC	intron_variant	Intron 1 of 1		XP_011512382.1
NDUFS6	NM_004553.6 link	c.-105_-104insG	upstream_gene_variant		ENST00000274137.10	NP_004544.1	O75380Q6IBC4
MRPL36	XM_017009751.3 link	c.-89_-88insC	upstream_gene_variant			XP_016865240.1	Q9P0J6

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
MRPL36	ENST00000505818.1 link	c.-13+20_-13+21insC	intron_variant	Intron 1 of 1	3		ENSP00000427152.1	Q9P0J6
NDUFS6	ENST00000274137.10 link	c.-105_-104insG	upstream_gene_variant		1	NM_004553.6	ENSP00000274137.6	O75380
NDUFS6	ENST00000469176.1 link	c.-105_-104insG	upstream_gene_variant		2		ENSP00000422557.1	D6RBT3
NDUFS6	ENST00000510329.1 link	n.-108_-107insG	upstream_gene_variant		3

Frequencies

GnomAD3 genomes

AF:

0.744

AC:

112743

AN:

151596

Hom.:

45195

Cov.:

show subpopulations

Gnomad AFR

AF:

0.437

Gnomad AMI

AF:

0.945

Gnomad AMR

AF:

0.844

Gnomad ASJ

AF:

0.847

Gnomad EAS

AF:

0.445

Gnomad SAS

AF:

0.730

Gnomad FIN

AF:

0.918

Gnomad MID

AF:

0.794

Gnomad NFE

AF:

0.895

Gnomad OTH

AF:

0.784

GnomAD4 exome

AF:

0.857

AC:

1138047

AN:

1328022

Hom.:

495183

Cov.:

AF XY:

0.855

AC XY:

553790

AN XY:

647774

show subpopulations

Gnomad4 AFR exome

AF:

0.418

Gnomad4 AMR exome

AF:

0.861

Gnomad4 ASJ exome

AF:

0.844

Gnomad4 EAS exome

AF:

0.479

Gnomad4 SAS exome

AF:

0.739

Gnomad4 FIN exome

AF:

0.913

Gnomad4 NFE exome

AF:

0.891

Gnomad4 OTH exome

AF:

0.818

GnomAD4 genome

AF:

0.743

AC:

112773

AN:

151712

Hom.:

45200

Cov.:

AF XY:

0.744

AC XY:

55121

AN XY:

74130

show subpopulations

Gnomad4 AFR

AF:

0.436

Gnomad4 AMR

AF:

0.844

Gnomad4 ASJ

AF:

0.847

Gnomad4 EAS

AF:

0.444

Gnomad4 SAS

AF:

0.730

Gnomad4 FIN

AF:

0.918

Gnomad4 NFE

AF:

0.895

Gnomad4 OTH

AF:

0.782

Alfa

AF:

0.743

Hom.:

1928

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Jun 23, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over