rs3736594

Positions:

• chr2-27772914-A-C
• chr2-27772914-A-G
• chr2-27772914-A-T

Variant summary

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

The NM_004891.4(MRPL33):​c.41+222A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.674 in 505,392 control chromosomes in the GnomAD database, including 118,462 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 0.62 (30844 hom., cov: 32)
  • Exomes 𝑓: 0.70 (87618 hom.)
• Consequence: MRPL33 NM_004891.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0300

Genes affected

MRPL33 (HGNC:14487): (mitochondrial ribosomal protein L33) 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. Alternatively spliced transcript variants encoding different isoforms have been described. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.735 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MRPL33	NM_004891.4	c.41+222A>C		intron_variant		ENST00000296102.8	NP_004882.1
MRPL33	NM_145330.3	c.41+222A>C		intron_variant			NP_663303.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MRPL33	ENST00000296102.8	c.41+222A>C		intron_variant		1	NM_004891.4	ENSP00000296102	P1

Frequencies

GnomAD3 genomes AF: 0.621 AC: 94428 AN: 151950 Hom.: 30851 Cov.: 32

Gnomad AFR AF: 0.442

Gnomad AMI AF: 0.582

Gnomad AMR AF: 0.558

Gnomad ASJ AF: 0.738

Gnomad EAS AF: 0.416

Gnomad SAS AF: 0.674

Gnomad FIN AF: 0.681

Gnomad MID AF: 0.775

Gnomad NFE AF: 0.741

Gnomad OTH AF: 0.654

GnomAD4 exome AF: 0.697 AC: 246301 AN: 353324 Hom.: 87618 AF XY: 0.699 AC XY: 130817 AN XY: 187178

Gnomad4 AFR exome AF: 0.434

Gnomad4 AMR exome AF: 0.519

Gnomad4 ASJ exome AF: 0.733

Gnomad4 EAS exome AF: 0.472

Gnomad4 SAS exome AF: 0.694

Gnomad4 FIN exome AF: 0.682

Gnomad4 NFE exome AF: 0.742

Gnomad4 OTH exome AF: 0.682

GnomAD4 genome AF: 0.621 AC: 94434 AN: 152068 Hom.: 30844 Cov.: 32 AF XY: 0.616 AC XY: 45777 AN XY: 74340

Gnomad4 AFR AF: 0.441

Gnomad4 AMR AF: 0.558

Gnomad4 ASJ AF: 0.738

Gnomad4 EAS AF: 0.416

Gnomad4 SAS AF: 0.674

Gnomad4 FIN AF: 0.681

Gnomad4 NFE AF: 0.741

Gnomad4 OTH AF: 0.656

Alfa AF: 0.704 Hom.: 31472

Bravo AF: 0.598

Asia WGS AF: 0.519 AC: 1807 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.4
DANN	Benign	0.73

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: rs3736594; hg19: chr2-27995781;