rs2339844

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_020409.3(MRPL47):ā€‹c.28T>Gā€‹(p.Cys10Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.086 in 1,614,094 control chromosomes in the GnomAD database, including 6,803 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: š‘“ 0.091 ( 689 hom., cov: 33)
Exomes š‘“: 0.085 ( 6114 hom. )

Consequence

MRPL47
NM_020409.3 missense

Scores

2
16

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.61
Variant links:
Genes affected
MRPL47 (HGNC:16652): (mitochondrial ribosomal protein L47) 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. This gene is immediately adjacent to the gene for BAF complex 53 kDa subunit protein a (BAF53a), in a tail-to-tail orientation. Two transcript variants encoding different protein isoforms have been identified. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.0014838278).
BA1
GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.164 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
MRPL47NM_020409.3 linkuse as main transcriptc.28T>G p.Cys10Gly missense_variant 1/7 ENST00000476781.6 NP_065142.2
MRPL47NM_177988.1 linkuse as main transcriptc.-157T>G 5_prime_UTR_variant 1/6 NP_817125.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
MRPL47ENST00000476781.6 linkuse as main transcriptc.28T>G p.Cys10Gly missense_variant 1/71 NM_020409.3 ENSP00000417602 P1Q9HD33-1
MRPL47ENST00000259038.6 linkuse as main transcriptc.28T>G p.Cys10Gly missense_variant 1/71 ENSP00000259038 Q9HD33-2
MRPL47ENST00000392659.2 linkuse as main transcriptc.-157T>G 5_prime_UTR_variant 1/61 ENSP00000376427 Q9HD33-3

Frequencies

GnomAD3 genomes
AF:
0.0910
AC:
13842
AN:
152168
Hom.:
686
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0956
Gnomad AMI
AF:
0.123
Gnomad AMR
AF:
0.124
Gnomad ASJ
AF:
0.0640
Gnomad EAS
AF:
0.112
Gnomad SAS
AF:
0.174
Gnomad FIN
AF:
0.0809
Gnomad MID
AF:
0.0796
Gnomad NFE
AF:
0.0759
Gnomad OTH
AF:
0.0894
GnomAD3 exomes
AF:
0.104
AC:
26214
AN:
251370
Hom.:
1626
AF XY:
0.105
AC XY:
14284
AN XY:
135876
show subpopulations
Gnomad AFR exome
AF:
0.0951
Gnomad AMR exome
AF:
0.171
Gnomad ASJ exome
AF:
0.0646
Gnomad EAS exome
AF:
0.102
Gnomad SAS exome
AF:
0.171
Gnomad FIN exome
AF:
0.0839
Gnomad NFE exome
AF:
0.0757
Gnomad OTH exome
AF:
0.0951
GnomAD4 exome
AF:
0.0854
AC:
124869
AN:
1461808
Hom.:
6114
Cov.:
32
AF XY:
0.0875
AC XY:
63651
AN XY:
727204
show subpopulations
Gnomad4 AFR exome
AF:
0.0983
Gnomad4 AMR exome
AF:
0.164
Gnomad4 ASJ exome
AF:
0.0645
Gnomad4 EAS exome
AF:
0.126
Gnomad4 SAS exome
AF:
0.170
Gnomad4 FIN exome
AF:
0.0824
Gnomad4 NFE exome
AF:
0.0748
Gnomad4 OTH exome
AF:
0.0844
GnomAD4 genome
AF:
0.0911
AC:
13867
AN:
152286
Hom.:
689
Cov.:
33
AF XY:
0.0942
AC XY:
7012
AN XY:
74458
show subpopulations
Gnomad4 AFR
AF:
0.0960
Gnomad4 AMR
AF:
0.124
Gnomad4 ASJ
AF:
0.0640
Gnomad4 EAS
AF:
0.112
Gnomad4 SAS
AF:
0.174
Gnomad4 FIN
AF:
0.0809
Gnomad4 NFE
AF:
0.0760
Gnomad4 OTH
AF:
0.0880
Alfa
AF:
0.0816
Hom.:
1544
Bravo
AF:
0.0920
TwinsUK
AF:
0.0723
AC:
268
ALSPAC
AF:
0.0695
AC:
268
ESP6500AA
AF:
0.0924
AC:
407
ESP6500EA
AF:
0.0785
AC:
675
ExAC
AF:
0.102
AC:
12341
Asia WGS
AF:
0.118
AC:
411
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.087
BayesDel_addAF
Benign
-0.57
T
BayesDel_noAF
Benign
-0.45
CADD
Benign
20
DANN
Benign
0.65
DEOGEN2
Benign
0.0072
T;.
Eigen
Benign
-0.45
Eigen_PC
Benign
-0.41
FATHMM_MKL
Benign
0.14
N
LIST_S2
Benign
0.44
T;T
MetaRNN
Benign
0.0015
T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Uncertain
2.1
M;M
MutationTaster
Benign
1.0
P;P;P
PrimateAI
Uncertain
0.48
T
PROVEAN
Benign
-1.4
N;N
REVEL
Benign
0.066
Sift
Benign
0.26
T;T
Sift4G
Benign
0.27
T;T
Polyphen
0.0020
B;B
Vest4
0.50
MPC
0.17
ClinPred
0.035
T
GERP RS
5.1
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.42
gMVP
0.62

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.090
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

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

Other links and lift over

dbSNP: rs2339844; hg19: chr3-179322385; COSMIC: COSV52019701; COSMIC: COSV52019701; API