Variant 17-81704178-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_002949.4(MRPL12):c.75-66T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0657 in 1,507,612 control chromosomes in the GnomAD database, including 4,288 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.067 ( 412 hom., cov: 33)

Exomes 𝑓: 0.066 ( 3876 hom. )

Consequence

MRPL12
NM_002949.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.97

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:

ENSG00000262660 (HGNC:):

ENSG00000262660 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BP6

Variant 17-81704178-T-C is Benign according to our data. Variant chr17-81704178-T-C is described in ClinVar as [Benign]. Clinvar id is 676743.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.208 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MRPL12	NM_002949.4 link	c.75-66T>C		intron_variant		ENST00000333676.8	NP_002940.2	P52815

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MRPL12	ENST00000333676.8 link	c.75-66T>C		intron_variant		1	NM_002949.4	ENSP00000333837.3		P52815
ENSG00000262660	ENST00000571730.1 link	c.75-66T>C		intron_variant		2		ENSP00000461324.1		B4DLN1

Frequencies

GnomAD3 genomes

AF:

0.0674

AC:

10237

AN:

151972

Hom.:

412

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0719

Gnomad AMI

AF:

0.158

Gnomad AMR

AF:

0.0562

Gnomad ASJ

AF:

0.0239

Gnomad EAS

AF:

0.218

Gnomad SAS

AF:

0.0822

Gnomad FIN

AF:

0.0536

Gnomad MID

AF:

0.0854

Gnomad NFE

AF:

0.0578

Gnomad OTH

AF:

0.0599

GnomAD4 exome

AF:

0.0655

AC:

88792

AN:

1355522

Hom.:

3876

AF XY:

0.0655

AC XY:

43687

AN XY:

666694

show subpopulations

Gnomad4 AFR exome

AF:

0.0702

Gnomad4 AMR exome

AF:

0.0460

Gnomad4 ASJ exome

AF:

0.0282

Gnomad4 EAS exome

AF:

0.262

Gnomad4 SAS exome

AF:

0.0729

Gnomad4 FIN exome

AF:

0.0484

Gnomad4 NFE exome

AF:

0.0598

Gnomad4 OTH exome

AF:

0.0661

GnomAD4 genome

AF:

0.0674

AC:

10245

AN:

152090

Hom.:

412

Cov.:

AF XY:

0.0675

AC XY:

5015

AN XY:

74348

show subpopulations

Gnomad4 AFR

AF:

0.0721

Gnomad4 AMR

AF:

0.0562

Gnomad4 ASJ

AF:

0.0239

Gnomad4 EAS

AF:

0.218

Gnomad4 SAS

AF:

0.0821

Gnomad4 FIN

AF:

0.0536

Gnomad4 NFE

AF:

0.0578

Gnomad4 OTH

AF:

0.0588

Alfa

AF:

0.0595

Hom.:

260

Bravo

AF:

0.0689

Asia WGS

AF:

0.150

AC:

521

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 16, 2018	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

1.6

DANN

Benign

0.76

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