2-27773064-G-A

Position:

• chr2-27773064-G-A

Variant summary

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

The ENST00000296102.8(MRPL33):​c.41+372G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.665 in 152,076 control chromosomes in the GnomAD database, including 34,540 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 0.67 (34540 hom., cov: 32)
• Consequence: MRPL33 ENST00000296102.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.332

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=-0.94).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.742 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MRPL33	NM_004891.4	c.41+372G>A		intron_variant		ENST00000296102.8	NP_004882.1
MRPL33	NM_145330.3	c.41+372G>A		intron_variant			NP_663303.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MRPL33	ENST00000296102.8	c.41+372G>A		intron_variant		1	NM_004891.4	ENSP00000296102	P1

Frequencies

GnomAD3 genomes AF: 0.666 AC: 101146 AN: 151958 Hom.: 34539 Cov.: 32

Gnomad AFR AF: 0.578

Gnomad AMI AF: 0.593

Gnomad AMR AF: 0.576

Gnomad ASJ AF: 0.754

Gnomad EAS AF: 0.415

Gnomad SAS AF: 0.677

Gnomad FIN AF: 0.698

Gnomad MID AF: 0.782

Gnomad NFE AF: 0.748

Gnomad OTH AF: 0.685

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

GnomAD4 genome AF: 0.665 AC: 101182 AN: 152076 Hom.: 34540 Cov.: 32 AF XY: 0.660 AC XY: 49097 AN XY: 74342

Gnomad4 AFR AF: 0.577

Gnomad4 AMR AF: 0.576

Gnomad4 ASJ AF: 0.754

Gnomad4 EAS AF: 0.415

Gnomad4 SAS AF: 0.677

Gnomad4 FIN AF: 0.698

Gnomad4 NFE AF: 0.748

Gnomad4 OTH AF: 0.687

Alfa AF: 0.728 Hom.: 86590

Bravo AF: 0.647

Asia WGS AF: 0.529 AC: 1842 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	7.6
DANN	Benign	0.32

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: rs3792252; hg19: chr2-27995931;