Genetic Variant MRPL19:c.658-9C>A (chr2-75655055-C-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBP6_Very_Strong

The NM_014763.4(MRPL19):c.658-9C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0018 ( 0 hom., cov: 22)

Exomes 𝑓: 0.046 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

MRPL19
NM_014763.4 intron

Scores

Splicing: ADA: 0.0006152

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.574

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.67).

BP6

Variant 2-75655055-C-A is Benign according to our data. Variant chr2-75655055-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 726493.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MRPL19	NM_014763.4 link	c.658-9C>A		intron_variant	Intron 5 of 5	ENST00000393909.7	NP_055578.2	P49406

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MRPL19	ENST00000393909.7 link	c.658-9C>A		intron_variant	Intron 5 of 5	1	NM_014763.4	ENSP00000377486.2		P49406

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

148

AN:

81104

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.00206

Gnomad AMI

AF:

0.00211

Gnomad AMR

AF:

0.00262

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00842

Gnomad SAS

AF:

0.00586

Gnomad FIN

AF:

0.00362

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000889

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0459

AC:

28684

AN:

624820

Hom.:

Cov.:

AF XY:

0.0440

AC XY:

13937

AN XY:

316728

show subpopulations

Gnomad4 AFR exome

AF:

0.0456

Gnomad4 AMR exome

AF:

0.0180

Gnomad4 ASJ exome

AF:

0.0294

Gnomad4 EAS exome

AF:

0.0298

Gnomad4 SAS exome

AF:

0.0158

Gnomad4 FIN exome

AF:

0.0164

Gnomad4 NFE exome

AF:

0.0530

Gnomad4 OTH exome

AF:

0.0419

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00184

AC:

149

AN:

81148

Hom.:

Cov.:

AF XY:

0.00209

AC XY:

AN XY:

38306

show subpopulations

Gnomad4 AFR

AF:

0.00219

Gnomad4 AMR

AF:

0.00248

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00805

Gnomad4 SAS

AF:

0.00588

Gnomad4 FIN

AF:

0.00362

Gnomad4 NFE

AF:

0.000889

Gnomad4 OTH

AF:

0.00

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.67

CADD

Benign

DANN

Benign

0.68

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00062

dbscSNV1_RF

Benign

0.042

SpliceAI score (max)

0.14

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over