3-131469474-A-G

Position:

• chr3-131469474-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_007208.4(MRPL3):​c.816+222T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.012 in 149,646 control chromosomes in the GnomAD database, including 34 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: 𝑓 0.012 (34 hom., cov: 32)
• Consequence: MRPL3 NM_007208.4 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0270

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 3-131469474-A-G is Benign according to our data. Variant chr3-131469474-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 1217728.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0705 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MRPL3	NM_007208.4	c.816+222T>C		intron_variant		ENST00000264995.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MRPL3	ENST00000264995.8	c.816+222T>C		intron_variant		1	NM_007208.4	P1
MRPL3	ENST00000425847.6	c.897+222T>C		intron_variant		2
MRPL3	ENST00000511168.5	c.859+222T>C		intron_variant		2
MRPL3	ENST00000510043.1	n.240+222T>C		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.0120 AC: 1793 AN: 149526 Hom.: 32 Cov.: 32

Gnomad AFR AF: 0.0129

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0368

Gnomad ASJ AF: 0.000290

Gnomad EAS AF: 0.0771

Gnomad SAS AF: 0.0474

Gnomad FIN AF: 0.00292

Gnomad MID AF: 0.00357

Gnomad NFE AF: 0.000933

Gnomad OTH AF: 0.0108

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0120 AC: 1802 AN: 149646 Hom.: 34 Cov.: 32 AF XY: 0.0136 AC XY: 993 AN XY: 73074

Gnomad4 AFR AF: 0.0129

Gnomad4 AMR AF: 0.0374

Gnomad4 ASJ AF: 0.000290

Gnomad4 EAS AF: 0.0769

Gnomad4 SAS AF: 0.0474

Gnomad4 FIN AF: 0.00292

Gnomad4 NFE AF: 0.000933

Gnomad4 OTH AF: 0.0107

Alfa AF: 0.00807 Hom.: 12

Bravo AF: 0.0140

Asia WGS AF: 0.0680 AC: 237 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 15, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.1
DANN	Benign	0.76

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs16836769; hg19: chr3-131188318;