17-81704228-TGGG-T

Variant names:

• chr17-81704228-TGGG-T
• rs138172294
• NM_002949.4:c.75-13_75-11delGGG

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_002949.4(MRPL12):​c.75-13_75-11delGGG variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00333 in 1,593,968 control chromosomes in the GnomAD database, including 155 homozygotes. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.018 (84 hom., cov: 32)
  • Exomes 𝑓: 0.0018 (71 hom.)
• Consequence: MRPL12 NM_002949.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.67
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• combined oxidative phosphorylation deficiency 45

  Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ENSG00000262660 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -16 ACMG points.

• BP6: Variant 17-81704228-TGGG-T is Benign according to our data. Variant chr17-81704228-TGGG-T is described in ClinVar as Benign. ClinVar VariationId is 1298149.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.061 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002949.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MRPL12	NM_002949.4	MANE Select	c.75-13_75-11delGGG		intron	N/A	NP_002940.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MRPL12	ENST00000333676.8	TSL:1 MANE Select	c.75-15_75-13delGGG		intron	N/A	ENSP00000333837.3	P52815
	ENSG00000262660	ENST00000571730.1	TSL:2	c.75-15_75-13delGGG		intron	N/A	ENSP00000461324.1	B4DLN1
	MRPL12	ENST00000853971.1		c.75-15_75-13delGGG		intron	N/A	ENSP00000524030.1

Frequencies

GnomAD3 genomes AF: 0.0182 AC: 2764 AN: 151982 Hom.: 84 Cov.: 32

Gnomad AFR AF: 0.0631

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00754

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000191

Gnomad OTH AF: 0.0120

GnomAD2 exomes AF: 0.00499 AC: 1171 AN: 234566 AF XY: 0.00361

Gnomad AFR exome AF: 0.0668

Gnomad AMR exome AF: 0.00294

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000764

Gnomad OTH exome AF: 0.00123

GnomAD4 exome AF: 0.00176 AC: 2533 AN: 1441868 Hom.: 71 AF XY: 0.00154 AC XY: 1106 AN XY: 715974

African (AFR) AF: 0.0637 AC: 2095 AN: 32880

American (AMR) AF: 0.00339 AC: 143 AN: 42188

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25120

East Asian (EAS) AF: 0.00 AC: 0 AN: 39380

South Asian (SAS) AF: 0.000130 AC: 11 AN: 84500

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52310

Middle Eastern (MID) AF: 0.00336 AC: 14 AN: 4166

European-Non Finnish (NFE) AF: 0.0000408 AC: 45 AN: 1101936

Other (OTH) AF: 0.00379 AC: 225 AN: 59388

GnomAD4 genome AF: 0.0182 AC: 2769 AN: 152100 Hom.: 84 Cov.: 32 AF XY: 0.0174 AC XY: 1296 AN XY: 74342

African (AFR) AF: 0.0631 AC: 2615 AN: 41468

American (AMR) AF: 0.00753 AC: 115 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10590

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000191 AC: 13 AN: 67990

Other (OTH) AF: 0.0119 AC: 25 AN: 2108

Alfa AF: 0.00907 Hom.: 2

Bravo AF: 0.0204

Asia WGS AF: 0.00433 AC: 15 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.7
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs138172294; hg19: chr17-79671258;