NM_002949.4:c.74+37G>A

Variant names:

• chr17-81703612-G-A
• rs34724580
• NM_002949.4:c.74+37G>A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_002949.4(MRPL12):​c.74+37G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0665 in 1,354,568 control chromosomes in the GnomAD database, including 3,827 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.069 (430 hom., cov: 33)
  • Exomes 𝑓: 0.066 (3397 hom.)
• Consequence: MRPL12 NM_002949.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.23

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]

ENSG00000262660 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 17-81703612-G-A is Benign according to our data. Variant chr17-81703612-G-A is described in ClinVar as [Benign]. Clinvar id is 676742.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 rank	MANE	Protein	UniProt
MRPL12	NM_002949.4	c.74+37G>A		intron_variant	Intron 1 of 4	ENST00000333676.8	NP_002940.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MRPL12	ENST00000333676.8	c.74+37G>A		intron_variant	Intron 1 of 4	1	NM_002949.4	ENSP00000333837.3
ENSG00000262660	ENST00000571730.1	c.74+37G>A		intron_variant	Intron 1 of 14	2		ENSP00000461324.1

Frequencies

GnomAD3 genomes AF: 0.0687 AC: 10453 AN: 152136 Hom.: 430 Cov.: 33

Gnomad AFR AF: 0.0768

Gnomad AMI AF: 0.158

Gnomad AMR AF: 0.0563

Gnomad ASJ AF: 0.0242

Gnomad EAS AF: 0.218

Gnomad SAS AF: 0.0826

Gnomad FIN AF: 0.0535

Gnomad MID AF: 0.0860

Gnomad NFE AF: 0.0578

Gnomad OTH AF: 0.0626

GnomAD3 exomes AF: 0.0926 AC: 646 AN: 6978 Hom.: 41 AF XY: 0.0924 AC XY: 396 AN XY: 4286

Gnomad AFR exome AF: 0.0804

Gnomad AMR exome AF: 0.0755

Gnomad ASJ exome AF: 0.0511

Gnomad EAS exome AF: 0.275

Gnomad SAS exome AF: 0.126

Gnomad FIN exome AF: 0.0694

Gnomad NFE exome AF: 0.0877

Gnomad OTH exome AF: 0.0765

GnomAD4 exome AF: 0.0662 AC: 79605 AN: 1202322 Hom.: 3397 Cov.: 28 AF XY: 0.0663 AC XY: 38582 AN XY: 582062

Gnomad4 AFR exome AF: 0.0771

Gnomad4 AMR exome AF: 0.0524

Gnomad4 ASJ exome AF: 0.0294

Gnomad4 EAS exome AF: 0.280

Gnomad4 SAS exome AF: 0.0749

Gnomad4 FIN exome AF: 0.0498

Gnomad4 NFE exome AF: 0.0609

Gnomad4 OTH exome AF: 0.0674

GnomAD4 genome AF: 0.0687 AC: 10462 AN: 152246 Hom.: 430 Cov.: 33 AF XY: 0.0690 AC XY: 5139 AN XY: 74436

Gnomad4 AFR AF: 0.0770

Gnomad4 AMR AF: 0.0562

Gnomad4 ASJ AF: 0.0242

Gnomad4 EAS AF: 0.218

Gnomad4 SAS AF: 0.0825

Gnomad4 FIN AF: 0.0535

Gnomad4 NFE AF: 0.0578

Gnomad4 OTH AF: 0.0615

Alfa AF: 0.0594 Hom.: 30

Bravo AF: 0.0702

Asia WGS AF: 0.151 AC: 523 AN: 3474

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Jun 16, 2018

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. -

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Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.24
DANN	Benign	0.82
RBP_binding_hub_radar		0.85
RBP_regulation_power_radar		2.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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

Other links and lift over

dbSNP: rs34724580; hg19: chr17-79670642;