Variant 17-81703508-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_002949.4(MRPL12):c.7C>T(p.Pro3Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000203 in 1,485,278 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0011 ( 1 hom., cov: 33)

Exomes 𝑓: 0.00011 ( 0 hom. )

Consequence

MRPL12
NM_002949.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.884

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 Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.004731953).

BP6

Variant 17-81703508-C-T is Benign according to our data. Variant chr17-81703508-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2042837.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MRPL12	NM_002949.4 linkuse as main transcript	c.7C>T	p.Pro3Ser	missense_variant	1/5	ENST00000333676.8	NP_002940.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MRPL12	ENST00000333676.8 linkuse as main transcript	c.7C>T	p.Pro3Ser	missense_variant	1/5	1	NM_002949.4	ENSP00000333837	P1

Frequencies

GnomAD3 genomes

AF:

0.00106

AC:

161

AN:

152248

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00352

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000654

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:

0.0000147

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.000140

AC:

AN:

85754

Hom.:

AF XY:

0.000162

AC XY:

AN XY:

49478

show subpopulations

Gnomad AFR exome

AF:

0.00280

Gnomad AMR exome

AF:

0.000171

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000555

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000963

Gnomad OTH exome

AF:

0.000403

GnomAD4 exome

AF:

0.000106

AC:

141

AN:

1332912

Hom.:

Cov.:

AF XY:

0.0000867

AC XY:

AN XY:

657180

show subpopulations

Gnomad4 AFR exome

AF:

0.00357

Gnomad4 AMR exome

AF:

0.000136

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000402

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000123

Gnomad4 OTH exome

AF:

0.000398

GnomAD4 genome

AF:

0.00106

AC:

161

AN:

152366

Hom.:

Cov.:

AF XY:

0.00110

AC XY:

AN XY:

74512

show subpopulations

Gnomad4 AFR

AF:

0.00351

Gnomad4 AMR

AF:

0.000653

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.000452

Hom.:

Bravo

AF:

0.00121

ESP6500AA

AF:

0.00139

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000126

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Aug 10, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.088

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.24

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.030

T;.

Eigen

Benign

-0.53

Eigen_PC

Benign

-0.42

FATHMM_MKL

Benign

0.61

LIST_S2

Benign

0.48

T;T

M_CAP

Uncertain

0.13

MetaRNN

Benign

0.0047

T;T

MetaSVM

Benign

-0.70

MutationAssessor

Uncertain

2.4

M;.

MutationTaster

Benign

1.0

N;N

PROVEAN

Benign

-1.3

N;.

REVEL

Benign

0.039

Sift

Benign

0.030

D;.

Sift4G

Uncertain

0.035

D;D

Polyphen

0.16

B;.

Vest4

0.16

MVP

0.87

MPC

0.22

ClinPred

0.043

GERP RS

3.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.8

Varity_R

0.080

gMVP

0.37

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