Variant chr19-10259604-A-C details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_015956.3(MRPL4):c.740-13A>C 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 Benign (★★).

Frequency

Genomes: 𝑓 0.33 ( 0 hom., cov: 0)

Exomes 𝑓: 0.12 ( 240 hom. )

Failed GnomAD Quality Control

Consequence

MRPL4
NM_015956.3 splice_polypyrimidine_tract, intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.623

Variant links:

Genes affected

MRPL4 (HGNC:14276): (mitochondrial ribosomal protein L4) 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. Sequence analysis identified alternatively spliced variants that encode different protein isoforms. [provided by RefSeq, Jul 2008]

MRPL4 links:

(HGNC:):

links:

LIMASI (HGNC:56357): (lncRNA inflammatory and mucous response associated, antisense to ICAM1)

LIMASI 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=-0.83).

BP6

Variant 19-10259604-A-C is Benign according to our data. Variant chr19-10259604-A-C is described in ClinVar as [Benign]. Clinvar id is 403106.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE
MRPL4	NM_015956.3 linkuse as main transcript	c.740-13A>C	splice_polypyrimidine_tract_variant, intron_variant		ENST00000253099.11
MRPL4	NM_001411149.1 linkuse as main transcript	c.*98A>C	3_prime_UTR_variant	9/9
MRPL4	NM_146388.2 linkuse as main transcript	c.*866A>C	3_prime_UTR_variant	8/8
MRPL4	NM_146387.2 linkuse as main transcript	c.740-13A>C	splice_polypyrimidine_tract_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Appris	UniProt
MRPL4	ENST00000253099.11 linkuse as main transcript	c.740-13A>C	splice_polypyrimidine_tract_variant, intron_variant	1	NM_015956.3	P1	Q9BYD3-1
	ENST00000587088.1 linkuse as main transcript	n.222+220T>G	intron_variant, non_coding_transcript_variant	2
LIMASI	ENST00000592893.1 linkuse as main transcript	n.358+608T>G	intron_variant, non_coding_transcript_variant	3

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

8001

AN:

24390

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.302

Gnomad AMI

AF:

0.457

Gnomad AMR

AF:

0.193

Gnomad ASJ

AF:

0.400

Gnomad EAS

AF:

0.300

Gnomad SAS

AF:

0.318

Gnomad FIN

AF:

0.207

Gnomad MID

AF:

0.167

Gnomad NFE

AF:

0.408

Gnomad OTH

AF:

0.329

GnomAD3 exomes

AF:

0.431

AC:

23374

AN:

54276

Hom.:

AF XY:

0.430

AC XY:

12758

AN XY:

29658

show subpopulations

Gnomad AFR exome

AF:

0.383

Gnomad AMR exome

AF:

0.462

Gnomad ASJ exome

AF:

0.484

Gnomad EAS exome

AF:

0.435

Gnomad SAS exome

AF:

0.476

Gnomad FIN exome

AF:

0.448

Gnomad NFE exome

AF:

0.393

Gnomad OTH exome

AF:

0.454

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.121

AC:

37853

AN:

311844

Hom.:

240

Cov.:

AF XY:

0.137

AC XY:

20729

AN XY:

151840

show subpopulations

Gnomad4 AFR exome

AF:

0.173

Gnomad4 AMR exome

AF:

0.446

Gnomad4 ASJ exome

AF:

0.307

Gnomad4 EAS exome

AF:

0.199

Gnomad4 SAS exome

AF:

0.340

Gnomad4 FIN exome

AF:

0.337

Gnomad4 NFE exome

AF:

0.0749

Gnomad4 OTH exome

AF:

0.148

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR;InbreedingCoeff

AF:

0.328

AC:

8002

AN:

24406

Hom.:

Cov.:

AF XY:

0.300

AC XY:

3651

AN XY:

12160

show subpopulations

Gnomad4 AFR

AF:

0.302

Gnomad4 AMR

AF:

0.193

Gnomad4 ASJ

AF:

0.400

Gnomad4 EAS

AF:

0.297

Gnomad4 SAS

AF:

0.319

Gnomad4 FIN

AF:

0.207

Gnomad4 NFE

AF:

0.408

Gnomad4 OTH

AF:

0.327

Alfa

AF:

0.00374

Hom.:

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 29, 2016

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

3.1

DANN

Benign

0.68

Splicing

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