Variant 11-68903633-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The ENST00000362034.7(MRPL21):c.88+90T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00104 in 1,337,582 control chromosomes in the GnomAD database, including 13 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0051 ( 7 hom., cov: 33)

Exomes 𝑓: 0.00052 ( 6 hom. )

Consequence

MRPL21
ENST00000362034.7 intron

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.153

Variant links:

Genes affected

MRPL21 (HGNC:14479): (mitochondrial ribosomal protein L21) 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. Multiple transcript variants encoding different isoforms were identified through sequence analysis although some may be subject to nonsense-mediated decay (NMD). [provided by RefSeq, Jul 2008]

MRPL21 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 11-68903633-A-G is Benign according to our data. Variant chr11-68903633-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 1182091.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00511 (779/152350) while in subpopulation AFR AF= 0.0181 (754/41590). AF 95% confidence interval is 0.0171. There are 7 homozygotes in gnomad4. There are 361 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 7 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein
MRPL21	NM_181514.2 linkuse as main transcript	c.88+90T>C	intron_variant	ENST00000362034.7	NP_852615.1
MRPL21	NM_181515.2 linkuse as main transcript	c.-181+90T>C	intron_variant		NP_852616.1
MRPL21	XM_005273823.5 linkuse as main transcript	c.88+90T>C	intron_variant		XP_005273880.1
MRPL21	XR_247190.5 linkuse as main transcript	n.110+90T>C	intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MRPL21	ENST00000362034.7 linkuse as main transcript	c.88+90T>C		intron_variant		1	NM_181514.2	ENSP00000354580	P1	Q7Z2W9-1

Frequencies

GnomAD3 genomes

AF:

0.00510

AC:

777

AN:

152232

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0181

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00118

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00143

GnomAD4 exome

AF:

0.000521

AC:

617

AN:

1185232

Hom.:

AF XY:

0.000461

AC XY:

276

AN XY:

598662

show subpopulations

Gnomad4 AFR exome

AF:

0.0179

Gnomad4 AMR exome

AF:

0.000948

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000498

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000127

Gnomad4 OTH exome

AF:

0.00110

GnomAD4 genome

AF:

0.00511

AC:

779

AN:

152350

Hom.:

Cov.:

AF XY:

0.00485

AC XY:

361

AN XY:

74494

show subpopulations

Gnomad4 AFR

AF:

0.0181

Gnomad4 AMR

AF:

0.00118

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.00579

Hom.:

Bravo

AF:

0.00599

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 12, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

DANN

Benign

0.84

Splicing

Name

Calibrated prediction

Score

Prediction

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