chr2-75655273-G-A

Variant names:

• chr2-75655273-G-A
• rs17689863
• NM_014763.4:c.867G>A

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_014763.4(MRPL19):​c.867G>A​(p.Ser289Ser) 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
• Publications: 38 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014763.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MRPL19	NM_014763.4	MANE Select	c.867G>A	p.Ser289Ser	synonymous	Exon 6 of 6	NP_055578.2	P49406

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MRPL19	ENST00000393909.7	TSL:1 MANE Select	c.867G>A	p.Ser289Ser	synonymous	Exon 6 of 6	ENSP00000377486.2	P49406
	MRPL19	ENST00000409374.5	TSL:5	c.867G>A	p.Ser289Ser	synonymous	Exon 6 of 7	ENSP00000387284.1	P49406
	MRPL19	ENST00000884931.1		c.867G>A	p.Ser289Ser	synonymous	Exon 6 of 7	ENSP00000554990.1

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

GnomAD2 exomes AF: 0.243 AC: 60451 AN: 248332 AF XY: 0.246

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 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

African (AFR) AF: 0.0405 AC: 1351 AN: 33374

American (AMR) AF: 0.288 AC: 12844 AN: 44528

Ashkenazi Jewish (ASJ) AF: 0.206 AC: 5371 AN: 26078

East Asian (EAS) AF: 0.142 AC: 5620 AN: 39638

South Asian (SAS) AF: 0.272 AC: 23367 AN: 85934

European-Finnish (FIN) AF: 0.308 AC: 16440 AN: 53370

Middle Eastern (MID) AF: 0.155 AC: 873 AN: 5630

European-Non Finnish (NFE) AF: 0.252 AC: 279076 AN: 1109600

Other (OTH) AF: 0.221 AC: 13298 AN: 60264

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

African (AFR) AF: 0.0495 AC: 2054 AN: 41500

American (AMR) AF: 0.206 AC: 3143 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.208 AC: 720 AN: 3466

East Asian (EAS) AF: 0.151 AC: 777 AN: 5152

South Asian (SAS) AF: 0.272 AC: 1310 AN: 4816

European-Finnish (FIN) AF: 0.318 AC: 3345 AN: 10520

Middle Eastern (MID) AF: 0.163 AC: 48 AN: 294

European-Non Finnish (NFE) AF: 0.254 AC: 17249 AN: 67896

Other (OTH) AF: 0.181 AC: 381 AN: 2108

Alfa AF: 0.225 Hom.: 14142

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.013
DANN	Benign	0.56
PhyloP100		-2.2
PromoterAI		-0.0050	Neutral
Mutation Taster		=99/1	polymorphism (auto)

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

Other links and lift over

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