Variant 2-75655055-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The NM_014763.4(MRPL19):c.658-9C>T variant causes a splice polypyrimidine tract, 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 0.0098 ( 0 hom., cov: 22)

Exomes 𝑓: 0.011 ( 1 hom. )

Failed GnomAD Quality Control

Consequence

MRPL19
NM_014763.4 splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.00004051

Clinical Significance

Likely benign criteria provided, single submitter B:1

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 Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.72).

BP6

Variant 2-75655055-C-T is Benign according to our data. Variant chr2-75655055-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 769565.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MRPL19	NM_014763.4 linkuse as main transcript	c.658-9C>T		splice_polypyrimidine_tract_variant, intron_variant		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.658-9C>T		splice_polypyrimidine_tract_variant, intron_variant		1	NM_014763.4	ENSP00000377486	P1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

775

AN:

79386

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.00978

Gnomad AMI

AF:

0.0151

Gnomad AMR

AF:

0.00899

Gnomad ASJ

AF:

0.00386

Gnomad EAS

AF:

0.00573

Gnomad SAS

AF:

0.00591

Gnomad FIN

AF:

0.0342

Gnomad MID

AF:

0.0246

Gnomad NFE

AF:

0.00853

Gnomad OTH

AF:

0.0101

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0110

AC:

6938

AN:

630838

Hom.:

Cov.:

AF XY:

0.0120

AC XY:

3811

AN XY:

318736

show subpopulations

Gnomad4 AFR exome

AF:

0.0164

Gnomad4 AMR exome

AF:

0.0220

Gnomad4 ASJ exome

AF:

0.0153

Gnomad4 EAS exome

AF:

0.0163

Gnomad4 SAS exome

AF:

0.0434

Gnomad4 FIN exome

AF:

0.0137

Gnomad4 NFE exome

AF:

0.00766

Gnomad4 OTH exome

AF:

0.0121

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00976

AC:

775

AN:

79430

Hom.:

Cov.:

AF XY:

0.0105

AC XY:

394

AN XY:

37580

show subpopulations

Gnomad4 AFR

AF:

0.00975

Gnomad4 AMR

AF:

0.00912

Gnomad4 ASJ

AF:

0.00386

Gnomad4 EAS

AF:

0.00575

Gnomad4 SAS

AF:

0.00593

Gnomad4 FIN

AF:

0.0342

Gnomad4 NFE

AF:

0.00850

Gnomad4 OTH

AF:

0.0109

Alfa

AF:

0.0178

Hom.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Apr 09, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.72

CADD

Benign

DANN

Benign

0.73

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000041

dbscSNV1_RF

Benign

0.0

SpliceAI score (max)

0.0

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