2-27772914-A-T

Variant names:

• chr2-27772914-A-T
• rs3736594
• NM_004891.4:c.41+222A>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_004891.4(MRPL33):​c.41+222A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: MRPL33 NM_004891.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0300
• Publications: 38 publications found

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

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004891.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MRPL33	NM_004891.4	MANE Select	c.41+222A>T		intron	N/A	NP_004882.1	O75394-1
	MRPL33	NM_145330.3		c.41+222A>T		intron	N/A	NP_663303.1	O75394-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MRPL33	ENST00000296102.8	TSL:1 MANE Select	c.41+222A>T		intron	N/A	ENSP00000296102.3	O75394-1
	MRPL33	ENST00000379666.7	TSL:1	c.41+222A>T		intron	N/A	ENSP00000368988.3	O75394-2
	MRPL33	ENST00000883033.1		c.22+1115A>T		intron	N/A	ENSP00000553092.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 354236 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 187664

African (AFR) AF: 0.00 AC: 0 AN: 8896

American (AMR) AF: 0.00 AC: 0 AN: 10342

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 11194

East Asian (EAS) AF: 0.00 AC: 0 AN: 24156

South Asian (SAS) AF: 0.00 AC: 0 AN: 32344

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 24838

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1624

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 219938

Other (OTH) AF: 0.00 AC: 0 AN: 20904

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	3.2
DANN	Benign	0.77
PhyloP100		-0.030

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs3736594;

hg19: chr2-27995781;