1-228107668-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_ModerateBS1BS2

The NM_181463.3(MRPL55):​c.228G>A​(p.Ala76Ala) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00223 in 1,612,514 control chromosomes in the GnomAD database, including 79 homozygotes. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.012 ( 42 hom., cov: 33)
Exomes 𝑓: 0.0012 ( 37 hom. )

Consequence

MRPL55
NM_181463.3 splice_region, synonymous

Scores

2
Splicing: ADA: 0.9999
2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0130
Variant links:
Genes affected
MRPL55 (HGNC:16686): (mitochondrial ribosomal protein L55) 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. Multiple transcript variants encoding two different isoforms were identified through sequence analysis. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP6
Variant 1-228107668-C-T is Benign according to our data. Variant chr1-228107668-C-T is described in ClinVar as [Benign]. Clinvar id is 775678.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0118 (1792/152354) while in subpopulation AFR AF= 0.0412 (1711/41578). AF 95% confidence interval is 0.0395. There are 42 homozygotes in gnomad4. There are 849 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 42 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
MRPL55NM_181463.3 linkc.228G>A p.Ala76Ala splice_region_variant, synonymous_variant Exon 4 of 5 ENST00000336520.8 NP_852128.1 Q7Z7F7-1A0A024R3U3

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
MRPL55ENST00000336520.8 linkc.228G>A p.Ala76Ala splice_region_variant, synonymous_variant Exon 4 of 5 2 NM_181463.3 ENSP00000337342.3 Q7Z7F7-1

Frequencies

GnomAD3 genomes
AF:
0.0117
AC:
1787
AN:
152236
Hom.:
42
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0412
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00399
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000118
Gnomad OTH
AF:
0.00525
GnomAD3 exomes
AF:
0.00313
AC:
780
AN:
249512
Hom.:
22
AF XY:
0.00230
AC XY:
312
AN XY:
135370
show subpopulations
Gnomad AFR exome
AF:
0.0425
Gnomad AMR exome
AF:
0.00203
Gnomad ASJ exome
AF:
0.0000998
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000654
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000978
Gnomad OTH exome
AF:
0.00213
GnomAD4 exome
AF:
0.00123
AC:
1798
AN:
1460160
Hom.:
37
Cov.:
31
AF XY:
0.00108
AC XY:
784
AN XY:
726388
show subpopulations
Gnomad4 AFR exome
AF:
0.0434
Gnomad4 AMR exome
AF:
0.00221
Gnomad4 ASJ exome
AF:
0.0000765
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.000174
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000621
Gnomad4 OTH exome
AF:
0.00249
GnomAD4 genome
AF:
0.0118
AC:
1792
AN:
152354
Hom.:
42
Cov.:
33
AF XY:
0.0114
AC XY:
849
AN XY:
74498
show subpopulations
Gnomad4 AFR
AF:
0.0412
Gnomad4 AMR
AF:
0.00399
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000118
Gnomad4 OTH
AF:
0.00520
Alfa
AF:
0.00215
Hom.:
14
Bravo
AF:
0.0132
Asia WGS
AF:
0.00202
AC:
7
AN:
3478
EpiCase
AF:
0.000164
EpiControl
AF:
0.000178

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Jul 16, 2018
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.73
CADD
Benign
22
DANN
Benign
0.82
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Pathogenic
1.0
dbscSNV1_RF
Pathogenic
0.87
SpliceAI score (max)
0.48
Details are displayed if max score is > 0.2
DS_DG_spliceai
0.48
Position offset: -18

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs34055261; hg19: chr1-228295369; API