Variant chr19-10259609-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_015956.3(MRPL4):c.740-8G>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000232 in 426,084 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 2/2 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.00025 ( 0 hom., cov: 0)

Exomes 𝑓: 0.00023 ( 0 hom. )

Consequence

MRPL4
NM_015956.3 splice_region, intron

Scores

Splicing: ADA: 0.0001782

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.31

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:

ENSG00000267105 (HGNC:):

ENSG00000267105 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE	Protein	UniProt
MRPL4	NM_015956.3 linkuse as main transcript	c.740-8G>A	splice_region_variant, intron_variant		ENST00000253099.11	NP_057040.2	Q9BYD3-1A0A024R7C5
MRPL4	NM_001411149.1 linkuse as main transcript	c.*103G>A	3_prime_UTR_variant	9/9		NP_001398078.1
MRPL4	NM_146388.2 linkuse as main transcript	c.*871G>A	3_prime_UTR_variant	8/8		NP_666500.1	Q9BYD3-2
MRPL4	NM_146387.2 linkuse as main transcript	c.740-8G>A	splice_region_variant, intron_variant			NP_666499.1	Q9BYD3-1A0A024R7C5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MRPL4	ENST00000253099.11 linkuse as main transcript	c.740-8G>A		splice_region_variant, intron_variant		1	NM_015956.3	ENSP00000253099.5		Q9BYD3-1

Frequencies

GnomAD3 genomes

AF:

0.000252

AC:

AN:

27768

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00837

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000179

Gnomad OTH

AF:

0.00237

GnomAD3 exomes

AF:

0.000174

AC:

AN:

68894

Hom.:

AF XY:

0.000211

AC XY:

AN XY:

37844

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000371

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000328

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000231

AC:

AN:

398294

Hom.:

Cov.:

AF XY:

0.000277

AC XY:

AN XY:

194728

show subpopulations

Gnomad4 AFR exome

AF:

0.000105

Gnomad4 AMR exome

AF:

0.0000812

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00105

Gnomad4 SAS exome

AF:

0.000134

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000240

Gnomad4 OTH exome

AF:

0.000207

GnomAD4 genome

AF:

0.000252

AC:

AN:

27790

Hom.:

Cov.:

AF XY:

0.000424

AC XY:

AN XY:

14156

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00833

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000179

Gnomad4 OTH

AF:

0.00236

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

1.1

DANN

Benign

0.56

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00018

dbscSNV1_RF

Benign

0.074

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