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GeneBe

3-131468099-A-G

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_007208.4(MRPL3):c.886T>C(p.Leu296=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00203 in 1,561,654 control chromosomes in the GnomAD database, including 39 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.011 ( 26 hom., cov: 32)
Exomes 𝑓: 0.0011 ( 13 hom. )

Consequence

MRPL3
NM_007208.4 synonymous

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.30
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 -21 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.52).
BP6
Variant 3-131468099-A-G is Benign according to our data. Variant chr3-131468099-A-G is described in ClinVar as [Benign]. Clinvar id is 380562.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=1.3 with no splicing effect.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0105 (1605/152148) while in subpopulation AFR AF= 0.0352 (1462/41544). AF 95% confidence interval is 0.0337. There are 26 homozygotes in gnomad4. There are 781 alleles in male gnomad4 subpopulation. This position pass quality control queck.
BS2
High Homozygotes in GnomAd at 26 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
MRPL3NM_007208.4 linkuse as main transcriptc.886T>C p.Leu296= synonymous_variant 9/10 ENST00000264995.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
MRPL3ENST00000264995.8 linkuse as main transcriptc.886T>C p.Leu296= synonymous_variant 9/101 NM_007208.4 P1
MRPL3ENST00000425847.6 linkuse as main transcriptc.967T>C p.Leu323= synonymous_variant 10/112
MRPL3ENST00000511168.5 linkuse as main transcriptc.931T>C p.Leu311= synonymous_variant 9/102
MRPL3ENST00000510043.1 linkuse as main transcriptn.310T>C non_coding_transcript_exon_variant 3/42

Frequencies

GnomAD3 genomes
AF:
0.0105
AC:
1603
AN:
152030
Hom.:
26
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0352
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00570
Gnomad ASJ
AF:
0.00346
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000414
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00316
Gnomad NFE
AF:
0.000250
Gnomad OTH
AF:
0.0115
GnomAD3 exomes
AF:
0.00277
AC:
595
AN:
214418
Hom.:
10
AF XY:
0.00228
AC XY:
266
AN XY:
116838
show subpopulations
Gnomad AFR exome
AF:
0.0340
Gnomad AMR exome
AF:
0.00210
Gnomad ASJ exome
AF:
0.00224
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000425
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000235
Gnomad OTH exome
AF:
0.000811
GnomAD4 exome
AF:
0.00111
AC:
1559
AN:
1409506
Hom.:
13
Cov.:
27
AF XY:
0.00105
AC XY:
739
AN XY:
701730
show subpopulations
Gnomad4 AFR exome
AF:
0.0358
Gnomad4 AMR exome
AF:
0.00263
Gnomad4 ASJ exome
AF:
0.00181
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000902
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000139
Gnomad4 OTH exome
AF:
0.00279
GnomAD4 genome
AF:
0.0105
AC:
1605
AN:
152148
Hom.:
26
Cov.:
32
AF XY:
0.0105
AC XY:
781
AN XY:
74402
show subpopulations
Gnomad4 AFR
AF:
0.0352
Gnomad4 AMR
AF:
0.00570
Gnomad4 ASJ
AF:
0.00346
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000415
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000250
Gnomad4 OTH
AF:
0.0114
Alfa
AF:
0.00538
Hom.:
7
Bravo
AF:
0.0121
Asia WGS
AF:
0.00203
AC:
7
AN:
3460

ClinVar

Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not specified Benign:1
Benign, criteria provided, single submitterclinical testingGeneDxFeb 24, 2016This 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. -
not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeJan 23, 2024- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.52
Cadd
Benign
8.3
Dann
Benign
0.53

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: rs149305040; hg19: chr3-131186943; API