NM_004891.4:c.41+222A>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0300

Publications

38 publications found
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 rank MANE Protein UniProt
MRPL33NM_004891.4 linkc.41+222A>C intron_variant Intron 2 of 3 ENST00000296102.8 NP_004882.1 O75394-1
MRPL33NM_145330.3 linkc.41+222A>C intron_variant Intron 2 of 2 NP_663303.1 O75394-2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
MRPL33ENST00000296102.8 linkc.41+222A>C intron_variant Intron 2 of 3 1 NM_004891.4 ENSP00000296102.3 O75394-1

Frequencies

GnomAD3 genomes
AF:
0.621
AC:
94428
AN:
151950
Hom.:
30851
Cov.:
32
show subpopulations
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
show subpopulations
African (AFR)
AF:
0.434
AC:
3851
AN:
8870
American (AMR)
AF:
0.519
AC:
5353
AN:
10310
Ashkenazi Jewish (ASJ)
AF:
0.733
AC:
8187
AN:
11174
East Asian (EAS)
AF:
0.472
AC:
11363
AN:
24078
South Asian (SAS)
AF:
0.694
AC:
22387
AN:
32270
European-Finnish (FIN)
AF:
0.682
AC:
16875
AN:
24754
Middle Eastern (MID)
AF:
0.758
AC:
1229
AN:
1622
European-Non Finnish (NFE)
AF:
0.742
AC:
162845
AN:
219398
Other (OTH)
AF:
0.682
AC:
14211
AN:
20848
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.508
Heterozygous variant carriers
0
3318
6637
9955
13274
16592
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Exome Hom
Variant carriers
0
524
1048
1572
2096
2620
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
AF:
0.621
AC:
94434
AN:
152068
Hom.:
30844
Cov.:
32
AF XY:
0.616
AC XY:
45777
AN XY:
74340
show subpopulations
African (AFR)
AF:
0.441
AC:
18261
AN:
41444
American (AMR)
AF:
0.558
AC:
8525
AN:
15284
Ashkenazi Jewish (ASJ)
AF:
0.738
AC:
2561
AN:
3472
East Asian (EAS)
AF:
0.416
AC:
2156
AN:
5184
South Asian (SAS)
AF:
0.674
AC:
3249
AN:
4824
European-Finnish (FIN)
AF:
0.681
AC:
7197
AN:
10568
Middle Eastern (MID)
AF:
0.776
AC:
228
AN:
294
European-Non Finnish (NFE)
AF:
0.741
AC:
50342
AN:
67976
Other (OTH)
AF:
0.656
AC:
1384
AN:
2110
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.503
Heterozygous variant carriers
0
1731
3462
5194
6925
8656
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
776
1552
2328
3104
3880
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.691
Hom.:
99699
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
PhyloP100
-0.030
Mutation Taster
=100/0
polymorphism (auto)

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

Other links and lift over

dbSNP: rs3736594; hg19: chr2-27995781; API