Variant chr17-81703666-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_002949.4(MRPL12):c.74+91G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00416 in 1,176,742 control chromosomes in the GnomAD database, including 171 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.019 ( 107 hom., cov: 33)

Exomes 𝑓: 0.0020 ( 64 hom. )

Consequence

MRPL12
NM_002949.4 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.906

Variant links:

Genes affected

MRPL12 (HGNC:10378): (mitochondrial ribosomal protein L12) 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 which forms homodimers. In prokaryotic ribosomes, two L7/L12 dimers and one L10 protein form the L8 protein complex. [provided by RefSeq, Jul 2008]

MRPL12 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 17-81703666-G-A is Benign according to our data. Variant chr17-81703666-G-A is described in ClinVar as [Benign]. Clinvar id is 1298037.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0636 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MRPL12	NM_002949.4 linkuse as main transcript	c.74+91G>A		intron_variant		ENST00000333676.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MRPL12	ENST00000333676.8 linkuse as main transcript	c.74+91G>A		intron_variant		1	NM_002949.4	P1

Frequencies

GnomAD3 genomes

AF:

0.0189

AC:

2879

AN:

152164

Hom.:

103

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0653

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00753

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000621

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00637

Gnomad NFE

AF:

0.000279

Gnomad OTH

AF:

0.0163

GnomAD4 exome

AF:

0.00195

AC:

2000

AN:

1024468

Hom.:

AF XY:

0.00180

AC XY:

890

AN XY:

494944

show subpopulations

Gnomad4 AFR exome

AF:

0.0742

Gnomad4 AMR exome

AF:

0.00846

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000187

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000205

Gnomad4 OTH exome

AF:

0.00521

GnomAD4 genome

AF:

0.0191

AC:

2901

AN:

152274

Hom.:

107

Cov.:

AF XY:

0.0182

AC XY:

1358

AN XY:

74452

show subpopulations

Gnomad4 AFR

AF:

0.0657

Gnomad4 AMR

AF:

0.00745

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000279

Gnomad4 OTH

AF:

0.0161

Alfa

AF:

0.0152

Hom.:

Bravo

AF:

0.0225

Asia WGS

AF:

0.00491

AC:

AN:

3474

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

GeneDx

Jun 28, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

6.3

DANN

Benign

0.96

RBP_binding_hub_radar

0.85

RBP_regulation_power_radar

3.4

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