rs183772116

Variant names:

• chr17-81703666-G-A
• rs183772116
• NM_002949.4:c.74+91G>A

Your query was ambiguous. Multiple possible variants found:

• chr17-81703666-G-A
• chr17-81703666-G-C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_002949.4(MRPL12):​c.74+91G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00416 in 1,176,742 control chromosomes in the GnomAD database, including 171 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.019 (107 hom., cov: 33)
  • Exomes 𝑓: 0.0020 (64 hom.)
• Consequence: MRPL12 NM_002949.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.906
• 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 17-81703666-G-A is Benign according to our data. Variant chr17-81703666-G-A is described in ClinVar as Benign. ClinVar VariationId is 1298037.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0636 is higher than 0.05.

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.74+91G>A		intron	N/A	NP_002940.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MRPL12	ENST00000333676.8	TSL:1 MANE Select	c.74+91G>A		intron	N/A	ENSP00000333837.3	P52815
	ENSG00000262660	ENST00000571730.1	TSL:2	c.74+91G>A		intron	N/A	ENSP00000461324.1	B4DLN1
	MRPL12	ENST00000853971.1		c.74+91G>A		intron	N/A	ENSP00000524030.1

Frequencies

GnomAD3 genomes AF: 0.0189 AC: 2879 AN: 152164 Hom.: 103 Cov.: 33

Gnomad AFR AF: 0.0653

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00753

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00637

Gnomad NFE AF: 0.000279

Gnomad OTH AF: 0.0163

GnomAD4 exome AF: 0.00195 AC: 2000 AN: 1024468 Hom.: 64 AF XY: 0.00180 AC XY: 890 AN XY: 494944

African (AFR) AF: 0.0742 AC: 1515 AN: 20414

American (AMR) AF: 0.00846 AC: 70 AN: 8278

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14690

East Asian (EAS) AF: 0.00 AC: 0 AN: 25800

South Asian (SAS) AF: 0.000187 AC: 7 AN: 37374

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 26788

Middle Eastern (MID) AF: 0.00447 AC: 13 AN: 2908

European-Non Finnish (NFE) AF: 0.000205 AC: 173 AN: 845642

Other (OTH) AF: 0.00521 AC: 222 AN: 42574

GnomAD4 genome AF: 0.0191 AC: 2901 AN: 152274 Hom.: 107 Cov.: 33 AF XY: 0.0182 AC XY: 1358 AN XY: 74452

African (AFR) AF: 0.0657 AC: 2730 AN: 41562

American (AMR) AF: 0.00745 AC: 114 AN: 15300

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5168

South Asian (SAS) AF: 0.000414 AC: 2 AN: 4826

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

Middle Eastern (MID) AF: 0.00685 AC: 2 AN: 292

European-Non Finnish (NFE) AF: 0.000279 AC: 19 AN: 68002

Other (OTH) AF: 0.0161 AC: 34 AN: 2112

Alfa AF: 0.0180 Hom.: 6

Bravo AF: 0.0225

Asia WGS AF: 0.00491 AC: 17 AN: 3474

ClinVar

ClinVar submissions as Germline

Significance: 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
BayesDel_noAF	Benign	-0.80
CADD	Benign	6.3
DANN	Benign	0.96
PhyloP100		0.91
PromoterAI		-0.033	Neutral
RBP_binding_hub_radar		0.85
RBP_regulation_power_radar		3.4
Mutation Taster		=100/0	polymorphism (auto)

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: rs183772116; hg19: chr17-79670696;