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

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

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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MRPL12	NM_002949.4	c.75-13_75-11delGGG		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.75-15_75-13delGGG		intron_variant	Intron 1 of 4	1	NM_002949.4	ENSP00000333837.3
ENSG00000262660	ENST00000571730.1	c.75-15_75-13delGGG		intron_variant	Intron 1 of 14	2		ENSP00000461324.1

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

Gnomad4 AFR exome AF: 0.0637 AC: 2095 AN: 32880

Gnomad4 AMR exome AF: 0.00339 AC: 143 AN: 42188

Gnomad4 ASJ exome AF: 0.00 AC: 0 AN: 25120

Gnomad4 EAS exome AF: 0.00 AC: 0 AN: 39380

Gnomad4 SAS exome AF: 0.000130 AC: 11 AN: 84500

Gnomad4 FIN exome AF: 0.00 AC: 0 AN: 52310

Gnomad4 NFE exome AF: 0.0000408 AC: 45 AN: 1101936

Gnomad4 Remaining exome 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

Gnomad4 AFR AF: 0.0631 AC: 0.0630607 AN: 0.0630607

Gnomad4 AMR AF: 0.00753 AC: 0.00753407 AN: 0.00753407

Gnomad4 ASJ AF: 0.00 AC: 0 AN: 0

Gnomad4 EAS AF: 0.00 AC: 0 AN: 0

Gnomad4 SAS AF: 0.00 AC: 0 AN: 0

Gnomad4 FIN AF: 0.00 AC: 0 AN: 0

Gnomad4 NFE AF: 0.000191 AC: 0.000191205 AN: 0.000191205

Gnomad4 OTH AF: 0.0119 AC: 0.0118596 AN: 0.0118596

Alfa AF: 0.00907 Hom.: 2

Bravo AF: 0.0204

Asia WGS AF: 0.00433 AC: 15 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Jan 07, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Mar 22, 2016

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
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

Publications

LitVar

Other links and lift over

dbSNP: rs138172294; hg19: chr17-79671258;