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3-131462839-C-T

Variant summary

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

The NM_007208.4(MRPL3):c.931G>A(p.Gly311Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00333 in 1,611,402 control chromosomes in the GnomAD database, including 23 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0031 ( 3 hom., cov: 32)
Exomes 𝑓: 0.0034 ( 20 hom. )

Consequence

MRPL3
NM_007208.4 missense

Scores

19

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts U:1B:4

Conservation

PhyloP100: -0.237
Variant links:
Genes affected
MRPL3 (HGNC:10379): (mitochondrial ribosomal protein L3) 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 that belongs to the L3P ribosomal protein family. A pseudogene corresponding to this gene is found on chromosome 13q. [provided by RefSeq, Jul 2008]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.0067156255).
BP6
Variant 3-131462839-C-T is Benign according to our data. Variant chr3-131462839-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 374558.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS2
High Homozygotes in GnomAd at 3 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
MRPL3NM_007208.4 linkuse as main transcriptc.931G>A p.Gly311Ser missense_variant 10/10 ENST00000264995.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
MRPL3ENST00000264995.8 linkuse as main transcriptc.931G>A p.Gly311Ser missense_variant 10/101 NM_007208.4 P1
MRPL3ENST00000425847.6 linkuse as main transcriptc.1012G>A p.Gly338Ser missense_variant 11/112
MRPL3ENST00000511168.5 linkuse as main transcriptc.976G>A p.Gly326Ser missense_variant 10/102
MRPL3ENST00000510043.1 linkuse as main transcriptn.355G>A non_coding_transcript_exon_variant 4/42

Frequencies

GnomAD3 genomes
AF:
0.00314
AC:
477
AN:
152002
Hom.:
3
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000822
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00374
Gnomad ASJ
AF:
0.00288
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00394
Gnomad FIN
AF:
0.000189
Gnomad MID
AF:
0.0158
Gnomad NFE
AF:
0.00497
Gnomad OTH
AF:
0.00575
GnomAD3 exomes
AF:
0.00368
AC:
920
AN:
249772
Hom.:
7
AF XY:
0.00416
AC XY:
561
AN XY:
134998
show subpopulations
Gnomad AFR exome
AF:
0.00105
Gnomad AMR exome
AF:
0.00292
Gnomad ASJ exome
AF:
0.00278
Gnomad EAS exome
AF:
0.0000546
Gnomad SAS exome
AF:
0.00364
Gnomad FIN exome
AF:
0.00139
Gnomad NFE exome
AF:
0.00519
Gnomad OTH exome
AF:
0.00773
GnomAD4 exome
AF:
0.00335
AC:
4894
AN:
1459282
Hom.:
20
Cov.:
30
AF XY:
0.00354
AC XY:
2571
AN XY:
725978
show subpopulations
Gnomad4 AFR exome
AF:
0.00102
Gnomad4 AMR exome
AF:
0.00310
Gnomad4 ASJ exome
AF:
0.00288
Gnomad4 EAS exome
AF:
0.0000253
Gnomad4 SAS exome
AF:
0.00400
Gnomad4 FIN exome
AF:
0.00131
Gnomad4 NFE exome
AF:
0.00355
Gnomad4 OTH exome
AF:
0.00365
GnomAD4 genome
AF:
0.00312
AC:
475
AN:
152120
Hom.:
3
Cov.:
32
AF XY:
0.00313
AC XY:
233
AN XY:
74352
show subpopulations
Gnomad4 AFR
AF:
0.000819
Gnomad4 AMR
AF:
0.00373
Gnomad4 ASJ
AF:
0.00288
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00374
Gnomad4 FIN
AF:
0.000189
Gnomad4 NFE
AF:
0.00497
Gnomad4 OTH
AF:
0.00569
Alfa
AF:
0.00406
Hom.:
4
Bravo
AF:
0.00327
TwinsUK
AF:
0.00189
AC:
7
ALSPAC
AF:
0.00234
AC:
9
ESP6500AA
AF:
0.00136
AC:
6
ESP6500EA
AF:
0.00465
AC:
40
ExAC
AF:
0.00376
AC:
456
Asia WGS
AF:
0.00231
AC:
8
AN:
3476

ClinVar

Significance: Benign/Likely benign
Submissions summary: Uncertain:1Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Uncertain:1Benign:4
Likely benign, criteria provided, single submitterclinical testingCenter for Pediatric Genomic Medicine, Children's Mercy Hospital and ClinicsOct 13, 2016- -
Likely benign, criteria provided, single submitterclinical testingCeGaT Center for Human Genetics TuebingenDec 01, 2023MRPL3: BP4, BS2 -
Uncertain significance, no assertion criteria providedclinical testingMayo Clinic Laboratories, Mayo ClinicFeb 23, 2016- -
Benign, criteria provided, single submitterclinical testingGeneDxJul 11, 2019- -
Likely benign, criteria provided, single submitterclinical testingInvitaeJan 24, 2024- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.079
BayesDel_addAF
Benign
-0.58
T
BayesDel_noAF
Benign
-0.60
Cadd
Benign
4.5
Dann
Benign
0.55
DEOGEN2
Benign
0.014
T;T
Eigen
Benign
-1.1
Eigen_PC
Benign
-1.2
FATHMM_MKL
Benign
0.027
N
LIST_S2
Benign
0.29
T;T
M_CAP
Benign
0.0031
T
MetaRNN
Benign
0.0067
T;T
MetaSVM
Benign
-0.99
T
MutationAssessor
Benign
-1.1
N;.
MutationTaster
Benign
1.0
N;N
PrimateAI
Benign
0.32
T
PROVEAN
Benign
1.5
N;N
REVEL
Benign
0.017
Sift
Benign
0.79
T;T
Sift4G
Benign
0.73
T;T
Polyphen
0.0
B;B
Vest4
0.083
MVP
0.65
MPC
0.066
ClinPred
0.0020
T
GERP RS
-4.6
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.065
gMVP
0.22

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: rs148679749; hg19: chr3-131181683; COSMIC: COSV53916428; COSMIC: COSV53916428; API