rs58747104

Variant names:

• chr11-68903812-G-GCCGCCGCCATCTTC
• rs58747104
• NM_181514.2:c.-3_-2insGAAGATGGCGGCGG

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_181514.2(MRPL21):​c.-3_-2insGAAGATGGCGGCGG variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.308 in 1,611,806 control chromosomes in the GnomAD database, including 80,201 homozygotes. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.32 (8329 hom., cov: 0)
  • Exomes 𝑓: 0.31 (71872 hom.)
• Consequence: MRPL21 NM_181514.2 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0570
• Publications: 5 publications found

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]

IGHMBP2 Gene-Disease associations (from GenCC):

• autosomal recessive distal spinal muscular atrophy 1

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Ambry Genetics, Genomics England PanelApp, Orphanet, Labcorp Genetics (formerly Invitae)
• Charcot-Marie-Tooth disease axonal type 2S

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Ambry Genetics, Laboratory for Molecular Medicine, Orphanet, Labcorp Genetics (formerly Invitae)
• hereditary peripheral neuropathy

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP6: Variant 11-68903812-G-GCCGCCGCCATCTTC is Benign according to our data. Variant chr11-68903812-G-GCCGCCGCCATCTTC is described in ClinVar as Benign. ClinVar VariationId is 1245933.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.469 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_181514.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MRPL21	NM_181514.2	MANE Select	c.-3_-2insGAAGATGGCGGCGG		5_prime_UTR	Exon 1 of 7	NP_852615.1	Q7Z2W9-1
	MRPL21	NM_181515.2		c.-271_-270insGAAGATGGCGGCGG		5_prime_UTR	Exon 1 of 7	NP_852616.1	Q7Z2W9-2
	IGHMBP2	NM_002180.3	MANE Select	c.-141_-140insCCGCCGCCATCTTC		upstream_gene	N/A	NP_002171.2	P38935

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MRPL21	ENST00000362034.7	TSL:1 MANE Select	c.-3_-2insGAAGATGGCGGCGG		5_prime_UTR	Exon 1 of 7	ENSP00000354580.2	Q7Z2W9-1
	MRPL21	ENST00000918368.1		c.-3_-2insGAAGATGGCGGCGG		5_prime_UTR	Exon 1 of 6	ENSP00000588427.1
	MRPL21	ENST00000918367.1		c.-3_-2insGAAGATGGCGGCGG		5_prime_UTR	Exon 1 of 6	ENSP00000588426.1

Frequencies

GnomAD3 genomes AF: 0.322 AC: 49006 AN: 152004 Hom.: 8322 Cov.: 0

Gnomad AFR AF: 0.388

Gnomad AMI AF: 0.152

Gnomad AMR AF: 0.201

Gnomad ASJ AF: 0.368

Gnomad EAS AF: 0.215

Gnomad SAS AF: 0.485

Gnomad FIN AF: 0.366

Gnomad MID AF: 0.367

Gnomad NFE AF: 0.301

Gnomad OTH AF: 0.288

GnomAD4 exome AF: 0.306 AC: 447229 AN: 1459682 Hom.: 71872 Cov.: 45 AF XY: 0.314 AC XY: 227789 AN XY: 726076

African (AFR) AF: 0.395 AC: 13211 AN: 33452

American (AMR) AF: 0.142 AC: 6365 AN: 44706

Ashkenazi Jewish (ASJ) AF: 0.357 AC: 9323 AN: 26102

East Asian (EAS) AF: 0.246 AC: 9780 AN: 39690

South Asian (SAS) AF: 0.490 AC: 42267 AN: 86218

European-Finnish (FIN) AF: 0.376 AC: 19631 AN: 52190

Middle Eastern (MID) AF: 0.363 AC: 2087 AN: 5744

European-Non Finnish (NFE) AF: 0.293 AC: 325805 AN: 1111268

Other (OTH) AF: 0.311 AC: 18760 AN: 60312

GnomAD4 genome AF: 0.322 AC: 49049 AN: 152124 Hom.: 8329 Cov.: 0 AF XY: 0.327 AC XY: 24304 AN XY: 74380

African (AFR) AF: 0.388 AC: 16098 AN: 41502

American (AMR) AF: 0.201 AC: 3073 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.368 AC: 1274 AN: 3462

East Asian (EAS) AF: 0.215 AC: 1109 AN: 5164

South Asian (SAS) AF: 0.485 AC: 2341 AN: 4826

European-Finnish (FIN) AF: 0.366 AC: 3881 AN: 10604

Middle Eastern (MID) AF: 0.374 AC: 110 AN: 294

European-Non Finnish (NFE) AF: 0.300 AC: 20419 AN: 67952

Other (OTH) AF: 0.287 AC: 605 AN: 2110

Alfa AF: 0.239 Hom.: 742

Asia WGS AF: 0.353 AC: 1226 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.057
Mutation Taster		=300/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs58747104; hg19: chr11-68671280; COSMIC: COSV54826457; COSMIC: COSV54826457;