Variant 5-154941260-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_014180.4(MRPL22):c.72C>T(p.Ala24Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00902 in 1,613,068 control chromosomes in the GnomAD database, including 104 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0068 ( 6 hom., cov: 32)

Exomes 𝑓: 0.0093 ( 98 hom. )

Consequence

MRPL22
NM_014180.4 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.534

Variant links:

Genes affected

MRPL22 (HGNC:14480): (mitochondrial ribosomal protein L22) 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 that belongs to the L22 ribosomal protein family. A pseudogene corresponding to this gene is found on chromosome 4q. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

MRPL22 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.71).

BP6

Variant 5-154941260-C-T is Benign according to our data. Variant chr5-154941260-C-T is described in ClinVar as [Benign]. Clinvar id is 2655981.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.534 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 6 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MRPL22	NM_014180.4 linkuse as main transcript	c.72C>T	p.Ala24Ala	synonymous_variant	2/7	ENST00000523037.6	NP_054899.2	Q9NWU5-1
MRPL22	NM_001014990.3 linkuse as main transcript	c.-51C>T		5_prime_UTR_variant	2/6		NP_001014990.1	Q9NWU5-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MRPL22	ENST00000523037.6 linkuse as main transcript	c.72C>T	p.Ala24Ala	synonymous_variant	2/7	1	NM_014180.4	ENSP00000431040.1		Q9NWU5-1

Frequencies

GnomAD3 genomes

AF:

0.00678

AC:

1031

AN:

152102

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00167

Gnomad AMI

AF:

0.0351

Gnomad AMR

AF:

0.00518

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00145

Gnomad FIN

AF:

0.00811

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0110

Gnomad OTH

AF:

0.00432

GnomAD3 exomes

AF:

0.00660

AC:

1660

AN:

251440

Hom.:

AF XY:

0.00676

AC XY:

919

AN XY:

135894

show subpopulations

Gnomad AFR exome

AF:

0.00111

Gnomad AMR exome

AF:

0.00243

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00183

Gnomad FIN exome

AF:

0.00943

Gnomad NFE exome

AF:

0.0110

Gnomad OTH exome

AF:

0.00701

GnomAD4 exome

AF:

0.00925

AC:

13516

AN:

1460848

Hom.:

Cov.:

AF XY:

0.00902

AC XY:

6553

AN XY:

726656

show subpopulations

Gnomad4 AFR exome

AF:

0.00147

Gnomad4 AMR exome

AF:

0.00318

Gnomad4 ASJ exome

AF:

0.000306

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00177

Gnomad4 FIN exome

AF:

0.0120

Gnomad4 NFE exome

AF:

0.0108

Gnomad4 OTH exome

AF:

0.00806

GnomAD4 genome

AF:

0.00677

AC:

1031

AN:

152220

Hom.:

Cov.:

AF XY:

0.00672

AC XY:

500

AN XY:

74430

show subpopulations

Gnomad4 AFR

AF:

0.00166

Gnomad4 AMR

AF:

0.00517

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00145

Gnomad4 FIN

AF:

0.00811

Gnomad4 NFE

AF:

0.0110

Gnomad4 OTH

AF:

0.00428

Alfa

AF:

0.00823

Hom.:

Bravo

AF:

0.00630

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.00845

EpiControl

AF:

0.0106

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Mar 01, 2023

MRPL22: BP4, BP7, BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.71

CADD

Benign

7.6

DANN

Benign

0.75

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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