rs2839698

Positions:

• chr11-1997623-G-A
• chr11-1997623-G-C

Variant summary

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

The NM_001400176.1(MRPL23):​c.498-13918G>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)
• Consequence: MRPL23 NM_001400176.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.461

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.498-13918G>A		intron_variant			NP_001387105.1
MRPL23	XM_011520273.2	c.498-13918G>A		intron_variant			XP_011518575.1
H19	NR_002196.3	n.220C>T		non_coding_transcript_exon_variant	1/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
H19	ENST00000412788.6	n.220C>T		non_coding_transcript_exon_variant	1/5	1
H19	ENST00000414790.9	n.221C>T		non_coding_transcript_exon_variant	1/5	1
H19	ENST00000411861.6	n.220C>T		non_coding_transcript_exon_variant	1/4	2

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD3 exomes AF: 0.411 AC: 53912 AN: 131236 Hom.: 11985 AF XY: 0.411 AC XY: 29382 AN XY: 71544

Gnomad AFR exome AF: 0.101

Gnomad AMR exome AF: 0.378

Gnomad ASJ exome AF: 0.502

Gnomad EAS exome AF: 0.316

Gnomad SAS exome AF: 0.294

Gnomad FIN exome AF: 0.537

Gnomad NFE exome AF: 0.505

Gnomad OTH exome AF: 0.446

GnomAD4 exome Cov.: 0

GnomAD4 genome Cov.: 0

Alfa AF: 0.459 Hom.: 4573

Asia WGS AF: 0.276 AC: 959 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	3.9
DANN	Benign	0.44

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2839698; hg19: chr11-2018853; COSMIC: COSV66403896;