3-131468063-GA-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_007208.4(MRPL3):c.894+27del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.147 in 1,136,162 control chromosomes in the GnomAD database, including 10,040 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.12 (1344 hom., cov: 29)
  • Exomes 𝑓: 0.15 (8696 hom.)
• Consequence: MRPL3 NM_007208.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.70

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 -10 ACMG points.

• BP6: Variant 3-131468063-GA-G is Benign according to our data. Variant chr3-131468063-GA-G is described in ClinVar as [Benign]. Clinvar id is 1292149.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr3-131468063-GA-G is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.193 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MRPL3	NM_007208.4	c.894+27del		intron_variant		ENST00000264995.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MRPL3	ENST00000264995.8	c.894+27del		intron_variant		1	NM_007208.4	P1
MRPL3	ENST00000425847.6	c.975+27del		intron_variant		2
MRPL3	ENST00000511168.5	c.937+27del		intron_variant		2
MRPL3	ENST00000510043.1	n.318+27del		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.120 AC: 17410 AN: 145422 Hom.: 1342 Cov.: 29

Gnomad AFR AF: 0.0294

Gnomad AMI AF: 0.161

Gnomad AMR AF: 0.0820

Gnomad ASJ AF: 0.253

Gnomad EAS AF: 0.0652

Gnomad SAS AF: 0.203

Gnomad FIN AF: 0.167

Gnomad MID AF: 0.195

Gnomad NFE AF: 0.165

Gnomad OTH AF: 0.123

GnomAD3 exomes AF: 0.142 AC: 20961 AN: 147252 Hom.: 1036 AF XY: 0.149 AC XY: 12099 AN XY: 81446

Gnomad AFR exome AF: 0.0253

Gnomad AMR exome AF: 0.0505

Gnomad ASJ exome AF: 0.254

Gnomad EAS exome AF: 0.0364

Gnomad SAS exome AF: 0.192

Gnomad FIN exome AF: 0.167

Gnomad NFE exome AF: 0.162

Gnomad OTH exome AF: 0.143

GnomAD4 exome AF: 0.151 AC: 149891 AN: 990668 Hom.: 8696 Cov.: 12 AF XY: 0.153 AC XY: 76591 AN XY: 500828

Gnomad4 AFR exome AF: 0.0238

Gnomad4 AMR exome AF: 0.0578

Gnomad4 ASJ exome AF: 0.231

Gnomad4 EAS exome AF: 0.0715

Gnomad4 SAS exome AF: 0.184

Gnomad4 FIN exome AF: 0.165

Gnomad4 NFE exome AF: 0.156

Gnomad4 OTH exome AF: 0.141

GnomAD4 genome AF: 0.120 AC: 17412 AN: 145494 Hom.: 1344 Cov.: 29 AF XY: 0.121 AC XY: 8557 AN XY: 70780

Gnomad4 AFR AF: 0.0294

Gnomad4 AMR AF: 0.0819

Gnomad4 ASJ AF: 0.253

Gnomad4 EAS AF: 0.0654

Gnomad4 SAS AF: 0.203

Gnomad4 FIN AF: 0.167

Gnomad4 NFE AF: 0.165

Gnomad4 OTH AF: 0.126

Bravo AF: 0.102

Asia WGS AF: 0.135 AC: 466 AN: 3450

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 06, 2019

- -

Computational scores

Source: dbNSFP v4.3

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: rs374998359; hg19: chr3-131186907;