rs373040169

Variant names:

• chr17-81703456-C-T
• rs373040169
• NM_002949.4:c.-46C>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Moderate BP6_Moderate

The NM_002949.4(MRPL12):​c.-46C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000357 in 1,464,478 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00022 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00037 (0 hom.)
• Consequence: MRPL12 NM_002949.4 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.71
• 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.26).
• BP6: Variant 17-81703456-C-T is Benign according to our data. Variant chr17-81703456-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 385422.Status of the report is criteria_provided_single_submitter, 1 stars.

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.-46C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 5	NP_002940.2
	MRPL12	NM_002949.4	MANE Select	c.-46C>T		5_prime_UTR	Exon 1 of 5	NP_002940.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MRPL12	ENST00000333676.8	TSL:1 MANE Select	c.-46C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 5	ENSP00000333837.3	P52815
	ENSG00000262660	ENST00000571730.1	TSL:2	c.-46C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 15	ENSP00000461324.1	B4DLN1
	MRPL12	ENST00000333676.8	TSL:1 MANE Select	c.-46C>T		5_prime_UTR	Exon 1 of 5	ENSP00000333837.3	P52815

Frequencies

GnomAD3 genomes AF: 0.000223 AC: 34 AN: 152248 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000482

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000441

Gnomad OTH AF: 0.000957

GnomAD2 exomes AF: 0.000179 AC: 14 AN: 78094 AF XY: 0.000222

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000615

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000197

Gnomad NFE exome AF: 0.000394

Gnomad OTH exome AF: 0.000441

GnomAD4 exome AF: 0.000373 AC: 489 AN: 1312230 Hom.: 0 Cov.: 27 AF XY: 0.000363 AC XY: 235 AN XY: 647122

African (AFR) AF: 0.0000379 AC: 1 AN: 26378

American (AMR) AF: 0.000108 AC: 3 AN: 27780

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22870

East Asian (EAS) AF: 0.00 AC: 0 AN: 28740

South Asian (SAS) AF: 0.00 AC: 0 AN: 73284

European-Finnish (FIN) AF: 0.000150 AC: 5 AN: 33302

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4976

European-Non Finnish (NFE) AF: 0.000453 AC: 471 AN: 1040384

Other (OTH) AF: 0.000165 AC: 9 AN: 54516

GnomAD4 genome AF: 0.000223 AC: 34 AN: 152248 Hom.: 0 Cov.: 33 AF XY: 0.000188 AC XY: 14 AN XY: 74378

African (AFR) AF: 0.0000482 AC: 2 AN: 41468

American (AMR) AF: 0.00 AC: 0 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5200

South Asian (SAS) AF: 0.00 AC: 0 AN: 4838

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.000441 AC: 30 AN: 68042

Other (OTH) AF: 0.000957 AC: 2 AN: 2090

Alfa AF: 0.000324 Hom.: 2

Bravo AF: 0.000238

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.26
CADD	Benign	20
DANN	Benign	0.97
PhyloP100		1.7
PromoterAI		-0.17	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=296/4	polymorphism

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

Other links and lift over

dbSNP: rs373040169; hg19: chr17-79670486;