chr10-73250877-G-C

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_016065.4(MRPS16):ā€‹c.389C>Gā€‹(p.Thr130Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00421 in 1,614,068 control chromosomes in the GnomAD database, including 22 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā˜…ā˜…). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T130A) has been classified as Uncertain significance.

Frequency

Genomes: š‘“ 0.0033 ( 0 hom., cov: 32)
Exomes š‘“: 0.0043 ( 22 hom. )

Consequence

MRPS16
NM_016065.4 missense

Scores

2
17

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.819
Variant links:
Genes affected
MRPS16 (HGNC:14048): (mitochondrial ribosomal protein S16) 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 28S subunit protein that belongs to the ribosomal protein S16P family. The encoded protein is one of the most highly conserved ribosomal proteins between mammalian and yeast mitochondria. Three pseudogenes (located at 8q21.3, 20q13.32, 22q12-q13.1) for this gene have been described. [provided by RefSeq, Jul 2008]
DNAJC9-AS1 (HGNC:31432): (DNAJC9 and MRPS16 antisense RNA 1)

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.0038076937).
BP6
Variant 10-73250877-G-C is Benign according to our data. Variant chr10-73250877-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 214673.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS2
High Homozygotes in GnomAdExome4 at 22 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
MRPS16NM_016065.4 linkuse as main transcriptc.389C>G p.Thr130Arg missense_variant 3/3 ENST00000372945.8
DNAJC9-AS1NR_038373.1 linkuse as main transcriptn.175+2427G>C intron_variant, non_coding_transcript_variant
MRPS16XM_047425263.1 linkuse as main transcriptc.383C>G p.Thr128Arg missense_variant 3/3
MRPS16NM_001410935.1 linkuse as main transcriptc.274+886C>G intron_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
MRPS16ENST00000372945.8 linkuse as main transcriptc.389C>G p.Thr130Arg missense_variant 3/31 NM_016065.4 P1Q9Y3D3-1
DNAJC9-AS1ENST00000440197.2 linkuse as main transcriptn.182+2427G>C intron_variant, non_coding_transcript_variant 1

Frequencies

GnomAD3 genomes
AF:
0.00329
AC:
500
AN:
152192
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000844
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00386
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00186
Gnomad FIN
AF:
0.00179
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00547
Gnomad OTH
AF:
0.00287
GnomAD3 exomes
AF:
0.00323
AC:
811
AN:
251434
Hom.:
3
AF XY:
0.00339
AC XY:
461
AN XY:
135896
show subpopulations
Gnomad AFR exome
AF:
0.000984
Gnomad AMR exome
AF:
0.00223
Gnomad ASJ exome
AF:
0.0000992
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00193
Gnomad FIN exome
AF:
0.00130
Gnomad NFE exome
AF:
0.00534
Gnomad OTH exome
AF:
0.00375
GnomAD4 exome
AF:
0.00431
AC:
6299
AN:
1461758
Hom.:
22
Cov.:
31
AF XY:
0.00425
AC XY:
3087
AN XY:
727198
show subpopulations
Gnomad4 AFR exome
AF:
0.000657
Gnomad4 AMR exome
AF:
0.00244
Gnomad4 ASJ exome
AF:
0.000153
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00203
Gnomad4 FIN exome
AF:
0.00186
Gnomad4 NFE exome
AF:
0.00512
Gnomad4 OTH exome
AF:
0.00316
GnomAD4 genome
AF:
0.00328
AC:
500
AN:
152310
Hom.:
0
Cov.:
32
AF XY:
0.00317
AC XY:
236
AN XY:
74472
show subpopulations
Gnomad4 AFR
AF:
0.000842
Gnomad4 AMR
AF:
0.00386
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00186
Gnomad4 FIN
AF:
0.00179
Gnomad4 NFE
AF:
0.00547
Gnomad4 OTH
AF:
0.00284
Alfa
AF:
0.00391
Hom.:
0
Bravo
AF:
0.00302
TwinsUK
AF:
0.00485
AC:
18
ALSPAC
AF:
0.00285
AC:
11
ESP6500AA
AF:
0.00113
AC:
5
ESP6500EA
AF:
0.00523
AC:
45
ExAC
AF:
0.00327
AC:
397
Asia WGS
AF:
0.000866
AC:
3
AN:
3478
EpiCase
AF:
0.00491
EpiControl
AF:
0.00456

ClinVar

Significance: Likely benign
Submissions summary: Benign:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:4
Likely benign, criteria provided, single submitterclinical testingCeGaT Center for Human Genetics TuebingenJul 01, 2024DNAJC9-AS1: BS2; MRPS16: BP4, BS2 -
Likely benign, criteria provided, single submitterclinical testingGeneDxFeb 21, 2021- -
Likely benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpJan 22, 2024- -
Likely benign, no assertion criteria providedclinical testingMayo Clinic Laboratories, Mayo ClinicFeb 29, 2016- -
MRPS16-related disorder Benign:1
Likely benign, no assertion criteria providedclinical testingPreventionGenetics, part of Exact SciencesNov 11, 2019This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.097
BayesDel_addAF
Benign
-0.56
T
BayesDel_noAF
Benign
-0.57
CADD
Benign
17
DANN
Benign
0.80
DEOGEN2
Benign
0.0071
T
Eigen
Benign
-0.70
Eigen_PC
Benign
-0.73
FATHMM_MKL
Uncertain
0.79
D
LIST_S2
Benign
0.31
T
M_CAP
Benign
0.0055
T
MetaRNN
Benign
0.0038
T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
1.4
L
MutationTaster
Benign
1.0
N;N;N;N
PrimateAI
Uncertain
0.49
T
PROVEAN
Benign
-0.93
N
REVEL
Benign
0.12
Sift
Benign
0.18
T
Sift4G
Benign
0.40
T
Polyphen
0.013
B
Vest4
0.32
MVP
0.25
MPC
0.27
ClinPred
0.0037
T
GERP RS
0.59
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.0
Varity_R
0.11
gMVP
0.46

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

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

Other links and lift over

dbSNP: rs117510230; hg19: chr10-75010635; API