rs58747104

Variant names:

• chr11-68903812-G-GCCGCCACCATCTTC
• NM_181514.2:c.-3_-2insGAAGATGGTGGCGG

Your query was ambiguous. Multiple possible variants found:

• chr11-68903812-G-GCCGCCACCATCTTC
• chr11-68903812-G-GCCGCCATCTTC
• chr11-68903812-G-GCCGCCGCCATCTCC
• chr11-68903812-G-GCCGCCGCCATCTTC
• chr11-68903812-G-GCCGCCGCCATCTTT
• chr11-68903812-G-GCCGCCGCGATCTTC
• chr11-68903812-G-GCCGCCGGCATCTTC

Variant summary

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

The NM_181514.2(MRPL21):​c.-3_-2insGAAGATGGTGGCGG variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000753 in 1,460,090 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: 0)
  • Exomes 𝑓: 0.0000075 (0 hom.)
• Consequence: MRPL21 NM_181514.2 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0570

Genes affected

MRPL21 (HGNC:14479): (mitochondrial ribosomal protein L21) 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. Multiple transcript variants encoding different isoforms were identified through sequence analysis although some may be subject to nonsense-mediated decay (NMD). [provided by RefSeq, Jul 2008]

IGHMBP2 (HGNC:5542): (immunoglobulin mu DNA binding protein 2) This gene encodes a helicase superfamily member that binds a specific DNA sequence from the immunoglobulin mu chain switch region. Mutations in this gene lead to spinal muscle atrophy with respiratory distress type 1. [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
MRPL21	NM_181514.2	c.-3_-2insGAAGATGGTGGCGG		5_prime_UTR_variant	Exon 1 of 7	ENST00000362034.7	NP_852615.1
IGHMBP2	NM_002180.3	c.-141_-140insCCGCCACCATCTTC		upstream_gene_variant		ENST00000255078.8	NP_002171.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MRPL21	ENST00000362034.7	c.-3_-2insGAAGATGGTGGCGG		5_prime_UTR_variant	Exon 1 of 7	1	NM_181514.2	ENSP00000354580.2
IGHMBP2	ENST00000255078.8	c.-141_-140insCCGCCACCATCTTC		upstream_gene_variant		1	NM_002180.3	ENSP00000255078.4

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD4 exome AF: 0.00000753 AC: 11 AN: 1460090 Hom.: 0 Cov.: 45 AF XY: 0.00000688 AC XY: 5 AN XY: 726304

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: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000900

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 0

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: chr11-68671280;