rs2291382

chr3-131469684-T-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_007208.4(MRPL3):c.816+12A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.154 in 1,591,224 control chromosomes in the GnomAD database, including 21,091 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.12 (1459 hom., cov: 32)
  • Exomes 𝑓: 0.16 (19632 hom.)
• Consequence: MRPL3 NM_007208.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0340

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 3-131469684-T-G is Benign according to our data. Variant chr3-131469684-T-G is described in ClinVar as [Benign]. Clinvar id is 380042.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-131469684-T-G is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.218 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MRPL3	NM_007208.4	c.816+12A>C		intron_variant		ENST00000264995.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MRPL3	ENST00000264995.8	c.816+12A>C		intron_variant		1	NM_007208.4	P1

Frequencies

GnomAD3 genomes AF: 0.120 AC: 18238 AN: 152056 Hom.: 1457 Cov.: 32

Gnomad AFR AF: 0.0319

Gnomad AMI AF: 0.158

Gnomad AMR AF: 0.0814

Gnomad ASJ AF: 0.259

Gnomad EAS AF: 0.0631

Gnomad SAS AF: 0.229

Gnomad FIN AF: 0.163

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.164

Gnomad OTH AF: 0.123

GnomAD3 exomes AF: 0.146 AC: 35414 AN: 242578 Hom.: 3189 AF XY: 0.155 AC XY: 20359 AN XY: 131056

Gnomad AFR exome AF: 0.0287

Gnomad AMR exome AF: 0.0545

Gnomad ASJ exome AF: 0.266

Gnomad EAS exome AF: 0.0558

Gnomad SAS exome AF: 0.230

Gnomad FIN exome AF: 0.172

Gnomad NFE exome AF: 0.167

Gnomad OTH exome AF: 0.145

GnomAD4 exome AF: 0.158 AC: 227558 AN: 1439050 Hom.: 19632 Cov.: 27 AF XY: 0.162 AC XY: 115751 AN XY: 716578

Gnomad4 AFR exome AF: 0.0262

Gnomad4 AMR exome AF: 0.0582

Gnomad4 ASJ exome AF: 0.258

Gnomad4 EAS exome AF: 0.0692

Gnomad4 SAS exome AF: 0.229

Gnomad4 FIN exome AF: 0.174

Gnomad4 NFE exome AF: 0.161

Gnomad4 OTH exome AF: 0.150

GnomAD4 genome AF: 0.120 AC: 18243 AN: 152174 Hom.: 1459 Cov.: 32 AF XY: 0.121 AC XY: 9022 AN XY: 74410

Gnomad4 AFR AF: 0.0318

Gnomad4 AMR AF: 0.0814

Gnomad4 ASJ AF: 0.259

Gnomad4 EAS AF: 0.0632

Gnomad4 SAS AF: 0.229

Gnomad4 FIN AF: 0.163

Gnomad4 NFE AF: 0.164

Gnomad4 OTH AF: 0.127

Alfa AF: 0.160 Hom.: 4371

Bravo AF: 0.106

Asia WGS AF: 0.159 AC: 553 AN: 3474

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Dec 18, 2015

This 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 submitter

clinical testing

Invitae

Jan 30, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	4.1
Dann	Benign	0.61

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

Other links and lift over

dbSNP: rs2291382; hg19: chr3-131188528; COSMIC: COSV53914479; COSMIC: COSV53914479;