3-131468063-GAAA-GAAAAAA

Variant names:

• chr3-131468063-G-GAAA
• NM_007208.4:c.894+25_894+27dupTTT

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_007208.4(MRPL3):​c.894+25_894+27dupTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000101 in 994,222 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 29)
  • Exomes 𝑓: 0.0000010 (0 hom.)
• Consequence: MRPL3 NM_007208.4 intron
• Clinical Significance: Not reported in ClinVar
• 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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MRPL3	NM_007208.4	c.894+25_894+27dupTTT		intron_variant	Intron 9 of 9	ENST00000264995.8	NP_009139.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MRPL3	ENST00000264995.8	c.894+27_894+28insTTT		intron_variant	Intron 9 of 9	1	NM_007208.4	ENSP00000264995.2
MRPL3	ENST00000425847.6	c.975+27_975+28insTTT		intron_variant	Intron 10 of 10	2		ENSP00000398536.2
MRPL3	ENST00000511168.5	c.936+27_936+28insTTT		intron_variant	Intron 9 of 9	2		ENSP00000424107.1
MRPL3	ENST00000510043.1	n.318+27_318+28insTTT		intron_variant	Intron 3 of 3	2

Frequencies

GnomAD3 genomes Cov.: 29

GnomAD4 exome AF: 0.00000101 AC: 1 AN: 994222 Hom.: 0 Cov.: 12 AF XY: 0.00 AC XY: 0 AN XY: 502646

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000195

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 29

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-131186907;