rs10769945

Variant names:

• chr11-1963897-C-T
• rs10769945
• NM_001400176.1:c.298-8662C>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001400176.1(MRPL23):​c.298-8662C>T 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 0.43 (13393 hom., cov: 14)
  • Failed GnomAD Quality Control
• Consequence: MRPL23 NM_001400176.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.462
• Publications: 18 publications found

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]

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MRPL23	NM_001400176.1	c.298-8662C>T		intron_variant	Intron 4 of 6		NP_001387105.1
MRPL23	NM_001400179.1	c.298-8662C>T		intron_variant	Intron 4 of 5		NP_001387108.1
MRPL23	XM_011520273.2	c.298-8662C>T		intron_variant	Intron 4 of 6		XP_011518575.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MRPL23	ENST00000397297.7	c.298-8662C>T		intron_variant	Intron 4 of 5	2		ENSP00000380465.3
MRPL23	ENST00000397294.7	c.298-8662C>T		intron_variant	Intron 4 of 4	4		ENSP00000380462.3

Frequencies

GnomAD3 genomes AF: 0.433 AC: 47622 AN: 110098 Hom.: 13389 Cov.: 14

Gnomad AFR AF: 0.190

Gnomad AMI AF: 0.517

Gnomad AMR AF: 0.389

Gnomad ASJ AF: 0.619

Gnomad EAS AF: 0.463

Gnomad SAS AF: 0.456

Gnomad FIN AF: 0.585

Gnomad MID AF: 0.569

Gnomad NFE AF: 0.563

Gnomad OTH AF: 0.488

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

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.432 AC: 47639 AN: 110232 Hom.: 13393 Cov.: 14 AF XY: 0.431 AC XY: 22514 AN XY: 52204

African (AFR) AF: 0.190 AC: 6280 AN: 33138

American (AMR) AF: 0.389 AC: 3712 AN: 9548

Ashkenazi Jewish (ASJ) AF: 0.619 AC: 1548 AN: 2502

East Asian (EAS) AF: 0.463 AC: 1471 AN: 3176

South Asian (SAS) AF: 0.457 AC: 1031 AN: 2258

European-Finnish (FIN) AF: 0.585 AC: 3915 AN: 6690

Middle Eastern (MID) AF: 0.562 AC: 109 AN: 194

European-Non Finnish (NFE) AF: 0.563 AC: 28541 AN: 50672

Other (OTH) AF: 0.495 AC: 671 AN: 1356

Alfa AF: 0.411 Hom.: 18303

Asia WGS AF: 0.354 AC: 1233 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.73
DANN	Benign	0.46
PhyloP100		-0.46
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs10769945; hg19: chr11-1985127;