rs17689863

chr2-75655273-G-Achr2-75655273-G-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_014763.4(MRPL19):c.867G>A(p.Ser289=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.241 in 1,610,342 control chromosomes in the GnomAD database, including 49,468 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 0.19 (3551 hom., cov: 30)
  • Exomes 𝑓: 0.25 (45917 hom.)
• Consequence: MRPL19 NM_014763.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.17

Genes affected

MRPL19 (HGNC:14052): (mitochondrial ribosomal protein L19) 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. [provided by RefSeq, Jul 2008]

GCFC2 (HGNC:1317): (GC-rich sequence DNA-binding factor 2) The first mRNA transcript isolated for this gene was part of an artificial chimera derived from two distinct gene transcripts and a primer used in the cloning process (see Genbank accession M29204). A positively charged amino terminus present only in the chimera was determined to bind GC-rich DNA, thus mistakenly thought to identify a transcription factor gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP7: Synonymous conserved (PhyloP=-2.17 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.26 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MRPL19	NM_014763.4	c.867G>A	p.Ser289=	synonymous_variant	6/6	ENST00000393909.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MRPL19	ENST00000393909.7	c.867G>A	p.Ser289=	synonymous_variant	6/6	1	NM_014763.4	P1

Frequencies

GnomAD3 genomes AF: 0.192 AC: 29200 AN: 151806 Hom.: 3549 Cov.: 30

Gnomad AFR AF: 0.0495

Gnomad AMI AF: 0.201

Gnomad AMR AF: 0.205

Gnomad ASJ AF: 0.208

Gnomad EAS AF: 0.151

Gnomad SAS AF: 0.272

Gnomad FIN AF: 0.318

Gnomad MID AF: 0.165

Gnomad NFE AF: 0.254

Gnomad OTH AF: 0.182

GnomAD3 exomes AF: 0.243 AC: 60451 AN: 248332 Hom.: 8078 AF XY: 0.246 AC XY: 33150 AN XY: 134706

Gnomad AFR exome AF: 0.0422

Gnomad AMR exome AF: 0.303

Gnomad ASJ exome AF: 0.201

Gnomad EAS exome AF: 0.158

Gnomad SAS exome AF: 0.277

Gnomad FIN exome AF: 0.312

Gnomad NFE exome AF: 0.249

Gnomad OTH exome AF: 0.233

GnomAD4 exome AF: 0.246 AC: 358240 AN: 1458416 Hom.: 45917 Cov.: 34 AF XY: 0.246 AC XY: 178765 AN XY: 725600

Gnomad4 AFR exome AF: 0.0405

Gnomad4 AMR exome AF: 0.288

Gnomad4 ASJ exome AF: 0.206

Gnomad4 EAS exome AF: 0.142

Gnomad4 SAS exome AF: 0.272

Gnomad4 FIN exome AF: 0.308

Gnomad4 NFE exome AF: 0.252

Gnomad4 OTH exome AF: 0.221

GnomAD4 genome AF: 0.192 AC: 29210 AN: 151926 Hom.: 3551 Cov.: 30 AF XY: 0.195 AC XY: 14452 AN XY: 74244

Gnomad4 AFR AF: 0.0495

Gnomad4 AMR AF: 0.206

Gnomad4 ASJ AF: 0.208

Gnomad4 EAS AF: 0.151

Gnomad4 SAS AF: 0.272

Gnomad4 FIN AF: 0.318

Gnomad4 NFE AF: 0.254

Gnomad4 OTH AF: 0.181

Alfa AF: 0.232 Hom.: 9782

Bravo AF: 0.179

Asia WGS AF: 0.207 AC: 725 AN: 3476

EpiCase AF: 0.234

EpiControl AF: 0.240

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	0.013
Dann	Benign	0.56

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.12		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs17689863; hg19: chr2-75882399; COSMIC: COSV62567042; COSMIC: COSV62567042;