chr17-81703508-C-T

Variant names:

• chr17-81703508-C-T
• rs8074290
• NM_002949.4:c.7C>T

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_002949.4(MRPL12):​c.7C>T​(p.Pro3Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000203 in 1,485,278 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0011 (1 hom., cov: 33)
  • Exomes 𝑓: 0.00011 (0 hom.)
• Consequence: MRPL12 NM_002949.4 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.884
• Publications: 1 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 -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.004731953).
• BP6: Variant 17-81703508-C-T is Benign according to our data. Variant chr17-81703508-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2042837.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.7C>T	p.Pro3Ser	missense	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.7C>T	p.Pro3Ser	missense	Exon 1 of 5	ENSP00000333837.3	P52815
	ENSG00000262660	ENST00000571730.1	TSL:2	c.7C>T	p.Pro3Ser	missense	Exon 1 of 15	ENSP00000461324.1	B4DLN1
	MRPL12	ENST00000853971.1		c.7C>T	p.Pro3Ser	missense	Exon 1 of 5	ENSP00000524030.1

Frequencies

GnomAD3 genomes AF: 0.00106 AC: 161 AN: 152248 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.00352

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000654

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: 0.0000147

Gnomad OTH AF: 0.00191

GnomAD2 exomes AF: 0.000140 AC: 12 AN: 85754 AF XY: 0.000162

Gnomad AFR exome AF: 0.00280

Gnomad AMR exome AF: 0.000171

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000963

Gnomad OTH exome AF: 0.000403

GnomAD4 exome AF: 0.000106 AC: 141 AN: 1332912 Hom.: 0 Cov.: 31 AF XY: 0.0000867 AC XY: 57 AN XY: 657180

African (AFR) AF: 0.00357 AC: 96 AN: 26864

American (AMR) AF: 0.000136 AC: 4 AN: 29344

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23402

East Asian (EAS) AF: 0.00 AC: 0 AN: 29050

South Asian (SAS) AF: 0.0000402 AC: 3 AN: 74692

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33800

Middle Eastern (MID) AF: 0.000637 AC: 3 AN: 4710

European-Non Finnish (NFE) AF: 0.0000123 AC: 13 AN: 1055790

Other (OTH) AF: 0.000398 AC: 22 AN: 55260

GnomAD4 genome AF: 0.00106 AC: 161 AN: 152366 Hom.: 1 Cov.: 33 AF XY: 0.00110 AC XY: 82 AN XY: 74512

African (AFR) AF: 0.00351 AC: 146 AN: 41586

American (AMR) AF: 0.000653 AC: 10 AN: 15314

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: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68036

Other (OTH) AF: 0.00189 AC: 4 AN: 2114

Alfa AF: 0.000499 Hom.: 0

Bravo AF: 0.00121

ESP6500AA AF: 0.00139 AC: 4

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.000126 AC: 12

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.088
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.24
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.030	T
Eigen	Benign	-0.53
Eigen_PC	Benign	-0.42
FATHMM_MKL	Benign	0.61	D
LIST_S2	Benign	0.48	T
M_CAP	Uncertain	0.13	D
MetaRNN	Benign	0.0047	T
MetaSVM	Benign	-0.70	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		0.88
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.039
Sift	Benign	0.030	D
Sift4G	Uncertain	0.035	D
Polyphen		0.16	B
Vest4		0.16
MVP		0.87
MPC		0.22
ClinPred		0.043	T
GERP RS		3.0
PromoterAI		0.059	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.8
Varity_R		0.080
gMVP		0.37
Mutation Taster		=91/9	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: rs8074290; hg19: chr17-79670538;