dbSNP rs1635153: MRPL23:c.497+19085C>A (chr11-1991843-C-A) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001400176.1(MRPL23):c.497+19085C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000022 ( 0 hom., cov: 18)

Failed GnomAD Quality Control

Consequence

MRPL23
NM_001400176.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0730

Publications

6 publications found

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:

LINC01219 (HGNC:49653): (long intergenic non-protein coding RNA 1219)

LINC01219 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	Protein
MRPL23	NM_001400176.1 link	c.497+19085C>A	intron_variant	Intron 5 of 6	NP_001387105.1
LINC01219	NR_126400.1 link	n.165-95C>A	intron_variant	Intron 1 of 2
MRPL23	XM_011520273.2 link	c.497+19085C>A	intron_variant	Intron 5 of 6	XP_011518575.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL
LINC01219	ENST00000418612.3 link	n.271-95C>A	intron_variant	Intron 1 of 2	2
LINC01219	ENST00000733500.1 link	n.139-153C>A	intron_variant	Intron 2 of 3
LINC01219	ENST00000733501.1 link	n.293-75C>A	intron_variant	Intron 1 of 2
LINC01219	ENST00000733502.1 link	n.166-95C>A	intron_variant	Intron 1 of 2

Frequencies

GnomAD3 genomes

AF:

0.0000217

AC:

AN:

138006

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000250

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000110

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000164

Gnomad OTH

AF:

0.00

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000217

AC:

AN:

138006

Hom.:

Cov.:

AF XY:

0.0000301

AC XY:

AN XY:

66480

show subpopulations

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.0000250

AC:

AN:

39960

American (AMR)

AF:

0.00

AC:

AN:

13632

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3092

East Asian (EAS)

AF:

0.00

AC:

AN:

4808

South Asian (SAS)

AF:

0.00

AC:

AN:

3314

European-Finnish (FIN)

AF:

0.000110

AC:

AN:

9062

Middle Eastern (MID)

AF:

0.00

AC:

AN:

280

European-Non Finnish (NFE)

AF:

0.0000164

AC:

AN:

61132

Other (OTH)

AF:

0.00

AC:

AN:

1886

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.275

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

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:

0.123

Hom.:

633

Asia WGS

AF:

0.170

AC:

593

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

1.4

(source)

DANN

Benign

0.36

PhyloP100

0.073

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over