10-73250886-G-A

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBP6

The NM_016065.4(MRPS16):​c.380C>T​(p.Ala127Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000341 in 1,614,006 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000031 ( 0 hom. )

Consequence

MRPS16
NM_016065.4 missense

Scores

2
17

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:1

Conservation

PhyloP100: 0.993
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 Likely_benign. Variant got -3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.066274315).
BP6
Variant 10-73250886-G-A is Benign according to our data. Variant chr10-73250886-G-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 214672.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Uncertain_significance=1}.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
MRPS16NM_016065.4 linkuse as main transcriptc.380C>T p.Ala127Val missense_variant 3/3 ENST00000372945.8
DNAJC9-AS1NR_038373.1 linkuse as main transcriptn.175+2436G>A intron_variant, non_coding_transcript_variant
MRPS16XM_047425263.1 linkuse as main transcriptc.374C>T p.Ala125Val missense_variant 3/3
MRPS16NM_001410935.1 linkuse as main transcriptc.274+877C>T intron_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
MRPS16ENST00000372945.8 linkuse as main transcriptc.380C>T p.Ala127Val missense_variant 3/31 NM_016065.4 P1Q9Y3D3-1
DNAJC9-AS1ENST00000440197.2 linkuse as main transcriptn.182+2436G>A intron_variant, non_coding_transcript_variant 1

Frequencies

GnomAD3 genomes
AF:
0.0000657
AC:
10
AN:
152172
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000483
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000131
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000882
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000398
AC:
10
AN:
251456
Hom.:
0
AF XY:
0.0000441
AC XY:
6
AN XY:
135906
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000173
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000264
Gnomad OTH exome
AF:
0.000163
GnomAD4 exome
AF:
0.0000308
AC:
45
AN:
1461834
Hom.:
0
Cov.:
31
AF XY:
0.0000330
AC XY:
24
AN XY:
727224
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.000157
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000324
Gnomad4 OTH exome
AF:
0.0000331
GnomAD4 genome
AF:
0.0000657
AC:
10
AN:
152172
Hom.:
0
Cov.:
32
AF XY:
0.0000673
AC XY:
5
AN XY:
74334
show subpopulations
Gnomad4 AFR
AF:
0.0000483
Gnomad4 AMR
AF:
0.000131
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000882
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000580
Hom.:
0
Bravo
AF:
0.0000567
ExAC
AF:
0.0000330
AC:
4

ClinVar

Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:1
Revision: criteria provided, conflicting classifications
LINK: link

Submissions by phenotype

not provided Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpJul 04, 2023In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. ClinVar contains an entry for this variant (Variation ID: 214672). This variant has not been reported in the literature in individuals affected with MRPS16-related conditions. This variant is present in population databases (rs767062387, gnomAD 0.02%). This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 127 of the MRPS16 protein (p.Ala127Val). -
not specified Benign:1
Likely benign, criteria provided, single submitterclinical testingGeneDxOct 03, 2014This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.078
BayesDel_addAF
Benign
-0.45
T
BayesDel_noAF
Benign
-0.61
CADD
Benign
17
DANN
Uncertain
0.99
DEOGEN2
Benign
0.0039
T
Eigen
Benign
-0.37
Eigen_PC
Benign
-0.25
FATHMM_MKL
Uncertain
0.85
D
LIST_S2
Benign
0.65
T
M_CAP
Benign
0.0047
T
MetaRNN
Benign
0.066
T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
0.0
N
MutationTaster
Benign
1.0
D;D;D;D
PrimateAI
Benign
0.27
T
PROVEAN
Benign
-1.4
N
REVEL
Benign
0.067
Sift
Benign
0.035
D
Sift4G
Benign
0.19
T
Polyphen
0.020
B
Vest4
0.032
MVP
0.39
MPC
0.17
ClinPred
0.13
T
GERP RS
4.8
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.10
gMVP
0.38

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: rs767062387; hg19: chr10-75010644; API