17-81704178-T-C

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

2

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]

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=-0.91).
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
MRPL12NM_002949.4 linkc.75-66T>C intron_variant ENST00000333676.8 NP_002940.2 P52815

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
MRPL12ENST00000333676.8 linkc.75-66T>C intron_variant 1 NM_002949.4 ENSP00000333837.3 P52815
ENSG00000262660ENST00000571730.1 linkc.75-66T>C intron_variant 2 ENSP00000461324.1 B4DLN1

Frequencies

GnomAD3 genomes
AF:
0.0674
AC:
10237
AN:
151972
Hom.:
412
Cov.:
33
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.:
33
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 submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -
Benign, criteria provided, single submitterclinical testingGeneDxJun 16, 2018This 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.

Other links and lift over

dbSNP: rs35815547; hg19: chr17-79671208; COSMIC: COSV61268993; COSMIC: COSV61268993; API