17-81703472-A-G

Variant names:

• chr17-81703472-A-G
• rs550332320
• NM_002949.4:c.-30A>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_002949.4(MRPL12):​c.-30A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000753 in 1,328,000 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.5e-7 (0 hom.)
• Consequence: MRPL12 NM_002949.4 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.576
• 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 -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.52).

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.-30A>G		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.-30A>G		5_prime_UTR	Exon 1 of 5	ENSP00000333837.3	P52815
	ENSG00000262660	ENST00000571730.1	TSL:2	c.-30A>G		5_prime_UTR	Exon 1 of 15	ENSP00000461324.1	B4DLN1
	MRPL12	ENST00000853971.1		c.-30A>G		5_prime_UTR	Exon 1 of 5	ENSP00000524030.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.53e-7 AC: 1 AN: 1328000 Hom.: 0 Cov.: 30 AF XY: 0.00000153 AC XY: 1 AN XY: 654794

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 26810

American (AMR) AF: 0.00 AC: 0 AN: 29380

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23392

East Asian (EAS) AF: 0.00 AC: 0 AN: 29028

South Asian (SAS) AF: 0.00 AC: 0 AN: 74672

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33636

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4968

European-Non Finnish (NFE) AF: 9.52e-7 AC: 1 AN: 1050958

Other (OTH) AF: 0.00 AC: 0 AN: 55156

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
CADD	Benign	13
DANN	Benign	0.87
PhyloP100		-0.58
PromoterAI		0.064	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs550332320; hg19: chr17-79670502;