Genetic Variant MRPL23:c.141-8G>A (chr11-1952119-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBP6_Very_Strong

The NM_021134.4(MRPL23):c.141-8G>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.00046 ( 0 hom., cov: 2)

Exomes 𝑓: 0.00028 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

MRPL23
NM_021134.4 splice_region, intron

Scores

Splicing: ADA: 0.00008258

Clinical Significance

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

Conservation

PhyloP100: -0.649

Variant links:

Genes affected

MRPL23 (HGNC:10322): (mitochondrial ribosomal protein L23) 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. The gene is biallelically expressed, despite its location within a region of imprinted genes on chromosome 11. [provided by RefSeq, Jul 2008]

MRPL23 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

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

BP6

Variant 11-1952119-G-A is Benign according to our data. Variant chr11-1952119-G-A is described in ClinVar as [Benign]. Clinvar id is 791542.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MRPL23	NM_021134.4 link	c.141-8G>A		splice_region_variant, intron_variant	Intron 2 of 4	ENST00000397298.8	NP_066957.3	Q16540A0A024RCB2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MRPL23	ENST00000397298.8 link	c.141-8G>A		splice_region_variant, intron_variant	Intron 2 of 4	1	NM_021134.4	ENSP00000380466.3		Q16540

Frequencies

GnomAD3 genomes

AF:

0.000456

AC:

AN:

17540

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.0159

Gnomad AMR

AF:

0.00101

Gnomad ASJ

AF:

0.00181

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000319

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00289

AC:

727

AN:

251328

AF XY:

0.00295

show subpopulations

Gnomad AFR exome

AF:

0.000862

Gnomad AMR exome

AF:

0.00437

Gnomad ASJ exome

AF:

0.0129

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000508

Gnomad NFE exome

AF:

0.00267

Gnomad OTH exome

AF:

0.00767

GnomAD4 exome

AF:

0.000277

AC:

AN:

97538

Hom.:

Cov.:

AF XY:

0.000271

AC XY:

AN XY:

51684

show subpopulations

Gnomad4 AFR exome

AF:

0.00

AC:

AN:

1472

Gnomad4 AMR exome

AF:

0.000309

AC:

AN:

3232

Gnomad4 ASJ exome

AF:

0.00142

AC:

AN:

2818

Gnomad4 EAS exome

AF:

0.00

AC:

AN:

3460

Gnomad4 SAS exome

AF:

0.000222

AC:

AN:

9006

Gnomad4 FIN exome

AF:

0.00

AC:

AN:

6710

Gnomad4 NFE exome

AF:

0.000215

AC:

AN:

65006

Gnomad4 Remaining exome

AF:

0.000555

AC:

AN:

5406

⚠️ The allele balance in gnomAD4 Exomes is highly skewed (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000456

AC:

AN:

17554

Hom.:

Cov.:

AF XY:

0.000258

AC XY:

AN XY:

7746

show subpopulations

Gnomad4 AFR

AF:

0.00

AC:

AN:

Gnomad4 AMR

AF:

0.00101

AC:

0.00100806

AN:

0.00100806

Gnomad4 ASJ

AF:

0.00181

AC:

0.00181159

AN:

0.00181159

Gnomad4 EAS

AF:

0.00

AC:

AN:

Gnomad4 SAS

AF:

0.00

AC:

AN:

Gnomad4 FIN

AF:

0.00

AC:

AN:

Gnomad4 NFE

AF:

0.000319

AC:

0.000318674

AN:

0.000318674

Gnomad4 OTH

AF:

0.00

AC:

AN:

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00300

Hom.:

Asia WGS

AF:

0.00202

AC:

AN:

3478

EpiCase

AF:

0.00382

EpiControl

AF:

0.00397

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Apr 12, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

0.24

DANN

Benign

0.73

Mutation Taster

=100/0

polymorphism

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000083

dbscSNV1_RF

Benign

0.014

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