rs217727

Positions:

• chr11-1995678-G-A

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001400176.1(MRPL23):​c.498-15863G>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: not found (cov: 0)
  • Failed GnomAD Quality Control
• Consequence: MRPL23 NM_001400176.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.397

Genes affected

H19 (HGNC:):

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]

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MRPL23	NM_001400176.1	c.498-15863G>A		intron_variant			NP_001387105.1
MRPL23	XM_011520273.2	c.498-15863G>A		intron_variant			XP_011518575.1
H19	NR_002196.3	n.1813C>T		non_coding_transcript_exon_variant	5/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
H19	ENST00000412788.6	n.1807C>T		non_coding_transcript_exon_variant	5/5	1
H19	ENST00000414790.9	n.1814C>T		non_coding_transcript_exon_variant	5/5	1
H19	ENST00000411861.6	n.1894C>T		non_coding_transcript_exon_variant	4/4	2

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD3 exomes AF: 0.204 AC: 46845 AN: 229874 Hom.: 5133 AF XY: 0.203 AC XY: 25717 AN XY: 126946

Gnomad AFR exome AF: 0.0860

Gnomad AMR exome AF: 0.249

Gnomad ASJ exome AF: 0.158

Gnomad EAS exome AF: 0.349

Gnomad SAS exome AF: 0.200

Gnomad FIN exome AF: 0.184

Gnomad NFE exome AF: 0.189

Gnomad OTH exome AF: 0.185

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

GnomAD4 genome Cov.: 0

Alfa AF: 0.188 Hom.: 5392

Asia WGS AF: 0.257 AC: 890 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	5.7
DANN	Benign	0.93

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs217727; hg19: chr11-2016908; COSMIC: COSV66403852;