17-81704268-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_002949.4(MRPL12):c.99C>T(p.Ala33Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00613 in 1,611,344 control chromosomes in the GnomAD database, including 54 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0048 ( 4 hom., cov: 32)

Exomes 𝑓: 0.0063 ( 50 hom. )

Consequence

MRPL12
NM_002949.4 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -3.44

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.66).

BP6

Variant 17-81704268-C-T is Benign according to our data. Variant chr17-81704268-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 381440.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-3.44 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MRPL12	NM_002949.4 link	c.99C>T	p.Ala33Ala	synonymous_variant	Exon 2 of 5	ENST00000333676.8	NP_002940.2	P52815

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MRPL12	ENST00000333676.8 link	c.99C>T	p.Ala33Ala	synonymous_variant	Exon 2 of 5	1	NM_002949.4	ENSP00000333837.3		P52815
ENSG00000262660	ENST00000571730.1 link	c.99C>T	p.Ala33Ala	synonymous_variant	Exon 2 of 15	2		ENSP00000461324.1		B4DLN1

Frequencies

GnomAD3 genomes

AF:

0.00477

AC:

726

AN:

152074

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00121

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.00223

Gnomad ASJ

AF:

0.0112

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00788

Gnomad FIN

AF:

0.0105

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00654

Gnomad OTH

AF:

0.00335

GnomAD2 exomes

AF:

0.00585

AC:

1454

AN:

248362

AF XY:

0.00588

show subpopulations

Gnomad AFR exome

AF:

0.000991

Gnomad AMR exome

AF:

0.00143

Gnomad ASJ exome

AF:

0.0100

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0123

Gnomad NFE exome

AF:

0.00743

Gnomad OTH exome

AF:

0.00759

GnomAD4 exome

AF:

0.00627

AC:

9154

AN:

1459152

Hom.:

Cov.:

AF XY:

0.00624

AC XY:

4531

AN XY:

725870

show subpopulations

Gnomad4 AFR exome

AF:

0.00105

AC:

AN:

33400

Gnomad4 AMR exome

AF:

0.00191

AC:

AN:

44468

Gnomad4 ASJ exome

AF:

0.0106

AC:

277

AN:

26042

Gnomad4 EAS exome

AF:

0.00

AC:

AN:

39696

Gnomad4 SAS exome

AF:

0.00529

AC:

455

AN:

86076

Gnomad4 FIN exome

AF:

0.0132

AC:

697

AN:

52990

Gnomad4 NFE exome

AF:

0.00654

AC:

7270

AN:

1111280

Gnomad4 Remaining exome

AF:

0.00546

AC:

329

AN:

60232

Heterozygous variant carriers

474

948

1422

1896

2370

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Exome Het

Exome Hom

Variant carriers

270

540

810

1080

1350

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00476

AC:

725

AN:

152192

Hom.:

Cov.:

AF XY:

0.00509

AC XY:

379

AN XY:

74404

show subpopulations

Gnomad4 AFR

AF:

0.00121

AC:

0.00120505

AN:

0.00120505

Gnomad4 AMR

AF:

0.00223

AC:

0.00222542

AN:

0.00222542

Gnomad4 ASJ

AF:

0.0112

AC:

0.0112327

AN:

0.0112327

Gnomad4 EAS

AF:

0.00

AC:

AN:

Gnomad4 SAS

AF:

0.00789

AC:

0.00789037

AN:

0.00789037

Gnomad4 FIN

AF:

0.0105

AC:

0.0104618

AN:

0.0104618

Gnomad4 NFE

AF:

0.00653

AC:

0.00652749

AN:

0.00652749

Gnomad4 OTH

AF:

0.00331

AC:

0.00331439

AN:

0.00331439

Heterozygous variant carriers

120

160

200

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

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:

0.00494

Hom.:

Bravo

AF:

0.00380

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.00464

EpiControl

AF:

0.00457

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

May 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

MRPL12: BP4, BP7, BS2 -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Jan 29, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:1

Dec 08, 2016

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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

-0.66

CADD

Benign

1.9

DANN

Benign

0.82

RBP_binding_hub_radar

0.92

RBP_regulation_power_radar

2.0

Mutation Taster

=100/0

polymorphism

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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