Variant 2-75655273-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.17

Variant links:

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]

MRPL19 links:

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]

GCFC2 links:

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ACMG classification

Classification made for transcript

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	Protein	UniProt
MRPL19	NM_014763.4 linkuse as main transcript	c.867G>A	p.Ser289=	synonymous_variant	6/6	ENST00000393909.7	NP_055578.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MRPL19	ENST00000393909.7 linkuse as main transcript	c.867G>A	p.Ser289=	synonymous_variant	6/6	1	NM_014763.4	ENSP00000377486	P1

Frequencies

GnomAD3 genomes

AF:

0.192

AC:

29200

AN:

151806

Hom.:

3549

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.246

AC XY:

178765

AN XY:

725600

show subpopulations

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.:

AF XY:

0.195

AC XY:

14452

AN XY:

74244

show subpopulations

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over