11-1988847-T-G

Position:

• chr11-1988847-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_001400176.1(MRPL23):​c.497+16089T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00616 in 145,502 control chromosomes in the GnomAD database, including 15 homozygotes. 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 0.0062 (15 hom., cov: 21)
• Consequence: MRPL23 NM_001400176.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.44

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]

MRPL23-AS1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00616 (897/145502) while in subpopulation AFR AF= 0.021 (849/40400). AF 95% confidence interval is 0.0198. There are 15 homozygotes in gnomad4. There are 424 alleles in male gnomad4 subpopulation. Median coverage is 21. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 15 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MRPL23	NM_001400176.1	c.497+16089T>G		intron_variant			NP_001387105.1
MRPL23	XM_011520273.2	c.497+16089T>G		intron_variant			XP_011518575.1
MRPL23-AS1	NR_024471.1	n.95+979A>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MRPL23-AS1	ENST00000419080.3	n.168+979A>C		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.00612 AC: 889 AN: 145380 Hom.: 14 Cov.: 21

Gnomad AFR AF: 0.0209

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00220

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000399

Gnomad SAS AF: 0.000253

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000768

Gnomad OTH AF: 0.00403

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.00616 AC: 897 AN: 145502 Hom.: 15 Cov.: 21 AF XY: 0.00599 AC XY: 424 AN XY: 70728

Gnomad4 AFR AF: 0.0210

Gnomad4 AMR AF: 0.00219

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000400

Gnomad4 SAS AF: 0.000253

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000768

Gnomad4 OTH AF: 0.00398

Alfa AF: 0.0839 Hom.: 208

Asia WGS AF: 0.171 AC: 595 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.083
DANN	Benign	0.41

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1635150; hg19: chr11-2010077;