chr3-131480993-G-A

Position:

• chr3-131480993-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_007208.4(MRPL3):​c.629+6687C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0365 in 152,220 control chromosomes in the GnomAD database, including 159 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.037 (159 hom., cov: 32)
• Consequence: MRPL3 NM_007208.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.503

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0521 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MRPL3	NM_007208.4	c.629+6687C>T		intron_variant		ENST00000264995.8	NP_009139.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MRPL3	ENST00000264995.8	c.629+6687C>T		intron_variant		1	NM_007208.4	ENSP00000264995	P1
MRPL3	ENST00000425847.6	c.710+6687C>T		intron_variant		2		ENSP00000398536
MRPL3	ENST00000507669.5	c.314+6687C>T		intron_variant		3		ENSP00000422419
MRPL3	ENST00000511168.5	c.672+6687C>T		intron_variant		2		ENSP00000424107

Frequencies

GnomAD3 genomes AF: 0.0365 AC: 5559 AN: 152102 Hom.: 159 Cov.: 32

Gnomad AFR AF: 0.0100

Gnomad AMI AF: 0.0297

Gnomad AMR AF: 0.0413

Gnomad ASJ AF: 0.0357

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0135

Gnomad FIN AF: 0.0525

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.0535

Gnomad OTH AF: 0.0397

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

GnomAD4 genome AF: 0.0365 AC: 5557 AN: 152220 Hom.: 159 Cov.: 32 AF XY: 0.0361 AC XY: 2688 AN XY: 74404

Gnomad4 AFR AF: 0.0100

Gnomad4 AMR AF: 0.0413

Gnomad4 ASJ AF: 0.0357

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0137

Gnomad4 FIN AF: 0.0525

Gnomad4 NFE AF: 0.0535

Gnomad4 OTH AF: 0.0388

Alfa AF: 0.0474 Hom.: 94

Bravo AF: 0.0345

Asia WGS AF: 0.00779 AC: 27 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	6.7
DANN	Benign	0.72

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: rs13091744; hg19: chr3-131199837;