rs2285935

Variant names:

• chr11-1993416-G-A
• rs2285935
• NM_001400176.1:c.498-18125G>A

Variant summary

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

The NM_001400176.1(MRPL23):​c.498-18125G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. 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 0.031 (983 hom., cov: 14)
  • Failed GnomAD Quality Control
• Consequence: MRPL23 NM_001400176.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.513

Genes affected

MRPL23 (HGNC:10322): (mitochondrial ribosomal protein L23) 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. The gene is biallelically expressed, despite its location within a region of imprinted genes on chromosome 11. [provided by RefSeq, Jul 2008]

LINC01219 (HGNC:49653): (long intergenic non-protein coding RNA 1219)

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 = 0.0576 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MRPL23	NM_001400176.1	c.498-18125G>A		intron_variant	Intron 5 of 6		NP_001387105.1
MRPL23	XM_011520273.2	c.498-18125G>A		intron_variant	Intron 5 of 6		XP_011518575.1
LINC01219	NR_126400.1	n.669G>A		non_coding_transcript_exon_variant	Exon 3 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LINC01219	ENST00000418612.2	n.669G>A		non_coding_transcript_exon_variant	Exon 3 of 3	2

Frequencies

GnomAD3 genomes AF: 0.0310 AC: 2636 AN: 85152 Hom.: 984 Cov.: 14

Gnomad AFR AF: 0.00405

Gnomad AMI AF: 0.00408

Gnomad AMR AF: 0.0116

Gnomad ASJ AF: 0.0299

Gnomad EAS AF: 0.00477

Gnomad SAS AF: 0.00894

Gnomad FIN AF: 0.113

Gnomad MID AF: 0.0169

Gnomad NFE AF: 0.0600

Gnomad OTH AF: 0.0150

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.0309 AC: 2634 AN: 85248 Hom.: 983 Cov.: 14 AF XY: 0.0318 AC XY: 1304 AN XY: 41010

Gnomad4 AFR AF: 0.00404

Gnomad4 AMR AF: 0.0116

Gnomad4 ASJ AF: 0.0299

Gnomad4 EAS AF: 0.00478

Gnomad4 SAS AF: 0.00897

Gnomad4 FIN AF: 0.113

Gnomad4 NFE AF: 0.0599

Gnomad4 OTH AF: 0.0149

Alfa AF: 0.473 Hom.: 27268

Asia WGS AF: 0.279 AC: 971 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	6.9
DANN	Benign	0.69

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2285935; hg19: chr11-2014646;