Variant 17-38298603-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_ModerateBP6_Moderate

The NM_032351.6(MRPL45):c.221G>A(p.Arg74His) variant causes a missense change. The variant allele was found at a frequency of 0.000267 in 1,612,342 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/16 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00019 ( 0 hom., cov: 29)

Exomes 𝑓: 0.00028 ( 0 hom. )

Consequence

MRPL45
NM_032351.6 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 3.73

Variant links:

Genes affected

MRPL45 (HGNC:16651): (mitochondrial ribosomal protein L45) 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. Alternative splicing results in multiple transcript variants. Pseudogenes corresponding to this gene are found on chromosomes 2p and 17q. [provided by RefSeq, May 2013]

MRPL45 links:

Genome browser will be placed here

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 (MetaRNN=0.09280467).

BP6

Variant 17-38298603-G-A is Benign according to our data. Variant chr17-38298603-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3207975.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MRPL45	NM_032351.6 linkuse as main transcript	c.221G>A	p.Arg74His	missense_variant	2/8	ENST00000613675.5	NP_115727.5
MRPL45	NM_001278279.3 linkuse as main transcript	c.221G>A	p.Arg74His	missense_variant	2/7		NP_001265208.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MRPL45	ENST00000613675.5 linkuse as main transcript	c.221G>A	p.Arg74His	missense_variant	2/8	1	NM_032351.6	ENSP00000484903	P1
MRPL45	ENST00000619548.1 linkuse as main transcript	c.221G>A	p.Arg74His	missense_variant	2/7	3		ENSP00000478397

Frequencies

GnomAD3 genomes

AF:

0.000185

AC:

AN:

151350

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000727

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000925

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000209

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000118

Gnomad OTH

AF:

0.000962

GnomAD3 exomes

AF:

0.000171

AC:

AN:

240044

Hom.:

AF XY:

0.000168

AC XY:

AN XY:

130984

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000566

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000176

Gnomad OTH exome

AF:

0.000510

GnomAD4 exome

AF:

0.000276

AC:

403

AN:

1460992

Hom.:

Cov.:

AF XY:

0.000244

AC XY:

177

AN XY:

726842

show subpopulations

Gnomad4 AFR exome

AF:

0.0000897

Gnomad4 AMR exome

AF:

0.000649

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000319

Gnomad4 OTH exome

AF:

0.000265

GnomAD4 genome

AF:

0.000185

AC:

AN:

151350

Hom.:

Cov.:

AF XY:

0.000203

AC XY:

AN XY:

73850

show subpopulations

Gnomad4 AFR

AF:

0.0000727

Gnomad4 AMR

AF:

0.000925

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000209

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000118

Gnomad4 OTH

AF:

0.000962

Bravo

AF:

0.000212

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000117

AC:

ExAC

AF:

0.0000909

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 29, 2023

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.087

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.34

CADD

Benign

DANN

Benign

0.94

Eigen

Benign

-0.62

Eigen_PC

Benign

-0.65

FATHMM_MKL

Uncertain

0.76

LIST_S2

Benign

0.74

T;T

M_CAP

Benign

0.0054

MetaRNN

Benign

0.093

T;T

MetaSVM

Benign

-0.73

MutationTaster

Benign

0.94

PrimateAI

Benign

0.38

Sift4G

Uncertain

0.017

D;D

Vest4

0.31

MVP

0.27

ClinPred

0.098

GERP RS

3.3

gMVP

0.69

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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