rs11744596

chr5-69223464-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_033281.6(MRPS36):c.43-2874T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.447 in 151,642 control chromosomes in the GnomAD database, including 15,250 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.45 (15250 hom., cov: 31)
• Consequence: MRPS36 NM_033281.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.99

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.542 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MRPS36	NM_033281.6	c.43-2874T>G		intron_variant		ENST00000256441.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MRPS36	ENST00000256441.5	c.43-2874T>G		intron_variant		1	NM_033281.6	P1

Frequencies

GnomAD3 genomes AF: 0.447 AC: 67705 AN: 151522 Hom.: 15234 Cov.: 31

Gnomad AFR AF: 0.500

Gnomad AMI AF: 0.637

Gnomad AMR AF: 0.457

Gnomad ASJ AF: 0.367

Gnomad EAS AF: 0.458

Gnomad SAS AF: 0.560

Gnomad FIN AF: 0.392

Gnomad MID AF: 0.453

Gnomad NFE AF: 0.414

Gnomad OTH AF: 0.428

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.447 AC: 67753 AN: 151642 Hom.: 15250 Cov.: 31 AF XY: 0.450 AC XY: 33292 AN XY: 74018

Gnomad4 AFR AF: 0.499

Gnomad4 AMR AF: 0.457

Gnomad4 ASJ AF: 0.367

Gnomad4 EAS AF: 0.458

Gnomad4 SAS AF: 0.560

Gnomad4 FIN AF: 0.392

Gnomad4 NFE AF: 0.414

Gnomad4 OTH AF: 0.429

Alfa AF: 0.429 Hom.: 6721

Bravo AF: 0.449

Asia WGS AF: 0.529 AC: 1840 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	14
Dann	Benign	0.76

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

LitVar

Other links and lift over

dbSNP: rs11744596; hg19: chr5-68519291; COSMIC: COSV56507749;