17-81704268-C-T

Variant names:

• chr17-81704268-C-T
• rs148659191
• NM_002949.4:c.99C>T

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_002949.4(MRPL12):​c.99C>T​(p.Ala33Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00613 in 1,611,344 control chromosomes in the GnomAD database, including 54 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0048 (4 hom., cov: 32)
  • Exomes 𝑓: 0.0063 (50 hom.)
• Consequence: MRPL12 NM_002949.4 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -3.44
• 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 -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.66).
• BP6: Variant 17-81704268-C-T is Benign according to our data. Variant chr17-81704268-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 381440.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-3.44 with no splicing effect.
• BS2: High Homozygotes in GnomAd4 at 4 Unknown gene

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.99C>T	p.Ala33Ala	synonymous	Exon 2 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.99C>T	p.Ala33Ala	synonymous	Exon 2 of 5	ENSP00000333837.3
	ENSG00000262660	ENST00000571730.1	TSL:2	c.99C>T	p.Ala33Ala	synonymous	Exon 2 of 15	ENSP00000461324.1
	MRPL12	ENST00000853971.1		c.99C>T	p.Ala33Ala	synonymous	Exon 2 of 5	ENSP00000524030.1

Frequencies

GnomAD3 genomes AF: 0.00477 AC: 726 AN: 152074 Hom.: 4 Cov.: 32

Gnomad AFR AF: 0.00121

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.00223

Gnomad ASJ AF: 0.0112

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00788

Gnomad FIN AF: 0.0105

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00654

Gnomad OTH AF: 0.00335

GnomAD2 exomes AF: 0.00585 AC: 1454 AN: 248362 AF XY: 0.00588

Gnomad AFR exome AF: 0.000991

Gnomad AMR exome AF: 0.00143

Gnomad ASJ exome AF: 0.0100

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0123

Gnomad NFE exome AF: 0.00743

Gnomad OTH exome AF: 0.00759

GnomAD4 exome AF: 0.00627 AC: 9154 AN: 1459152 Hom.: 50 Cov.: 31 AF XY: 0.00624 AC XY: 4531 AN XY: 725870

African (AFR) AF: 0.00105 AC: 35 AN: 33400

American (AMR) AF: 0.00191 AC: 85 AN: 44468

Ashkenazi Jewish (ASJ) AF: 0.0106 AC: 277 AN: 26042

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.00529 AC: 455 AN: 86076

European-Finnish (FIN) AF: 0.0132 AC: 697 AN: 52990

Middle Eastern (MID) AF: 0.00121 AC: 6 AN: 4968

European-Non Finnish (NFE) AF: 0.00654 AC: 7270 AN: 1111280

Other (OTH) AF: 0.00546 AC: 329 AN: 60232

GnomAD4 genome AF: 0.00476 AC: 725 AN: 152192 Hom.: 4 Cov.: 32 AF XY: 0.00509 AC XY: 379 AN XY: 74404

African (AFR) AF: 0.00121 AC: 50 AN: 41492

American (AMR) AF: 0.00223 AC: 34 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.0112 AC: 39 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00789 AC: 38 AN: 4816

European-Finnish (FIN) AF: 0.0105 AC: 111 AN: 10610

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

European-Non Finnish (NFE) AF: 0.00653 AC: 444 AN: 68020

Other (OTH) AF: 0.00331 AC: 7 AN: 2112

Alfa AF: 0.00494 Hom.: 0

Bravo AF: 0.00380

Asia WGS AF: 0.000866 AC: 3 AN: 3478

EpiCase AF: 0.00464

EpiControl AF: 0.00457

ClinVar

ClinVar submissions as Germline

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	1.9
DANN	Benign	0.82
PhyloP100		-3.4
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.0
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs148659191; hg19: chr17-79671298;