Variant 5-69228385-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_033281.6(MRPS36):c.292C>A(p.Gln98Lys) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000208 in 1,442,448 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

MRPS36
NM_033281.6 missense, splice_region

Scores

Splicing: ADA: 0.005222

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.52

Variant links:

Genes affected

MRPS36 (HGNC:16631): (alpha-ketoglutarate dehydrogenase subunit 4) Mammalian mitochondrial ribosomal proteins are encoded by nuclear genes and help in protein synthesis within the mitochondrion. The mitochondrial ribosome (mitoribosome) consists 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 28S subunit protein. Pseudogenes corresponding to this gene are found on chromosomes 3p, 4q, 8p, 11q, 12q, and 20p. [provided by RefSeq, Jul 2008]

MRPS36 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.31977665).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MRPS36	NM_033281.6 linkuse as main transcript	c.292C>A	p.Gln98Lys	missense_variant, splice_region_variant	3/4	ENST00000256441.5	NP_150597.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
MRPS36	ENST00000256441.5 linkuse as main transcript	c.292C>A	p.Gln98Lys	missense_variant, splice_region_variant	3/4	1	NM_033281.6	ENSP00000256441	P1
MRPS36	ENST00000512880.5 linkuse as main transcript	c.97C>A	p.Gln33Lys	missense_variant, splice_region_variant	3/4	5		ENSP00000423659
MRPS36	ENST00000602380.1 linkuse as main transcript	c.97C>A	p.Gln33Lys	missense_variant, splice_region_variant	3/4	2		ENSP00000473310
MRPS36	ENST00000507022.1 linkuse as main transcript	n.272C>A		splice_region_variant, non_coding_transcript_exon_variant	2/3	3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000432

AC:

AN:

231430

Hom.:

AF XY:

0.00

AC XY:

AN XY:

125452

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000590

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000208

AC:

AN:

1442448

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

716768

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000510

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000256

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 17, 2022

The c.292C>A (p.Q98K) alteration is located in exon 3 (coding exon 3) of the MRPS36 gene. This alteration results from a C to A substitution at nucleotide position 292, causing the glutamine (Q) at amino acid position 98 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.74

BayesDel_addAF

Benign

-0.092

BayesDel_noAF

Benign

-0.19

CADD

Uncertain

DANN

Benign

0.88

DEOGEN2

Benign

0.40

T;.;.

Eigen

Uncertain

0.41

Eigen_PC

Uncertain

0.41

FATHMM_MKL

Uncertain

0.88

M_CAP

Benign

0.0050

MetaRNN

Benign

0.32

T;T;T

MetaSVM

Benign

-0.65

MutationAssessor

Benign

1.8

L;.;.

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.63

PROVEAN

Uncertain

-2.6

D;D;.

REVEL

Benign

0.17

Sift

Uncertain

0.010

D;D;.

Sift4G

Benign

0.081

T;T;T

Polyphen

0.97

D;.;.

Vest4

0.51

MutPred

0.25

Gain of methylation at Q98 (P = 0.0037);.;.;

MVP

0.24

MPC

0.51

ClinPred

0.66

GERP RS

4.8

Varity_R

0.60

gMVP

0.80

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0052

dbscSNV1_RF

Benign

0.17

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.

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