3-131468063-GAAA-GAA

Variant names:

• chr3-131468063-GA-G
• rs374998359
• NM_007208.4:c.894+27delT

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_007208.4(MRPL3):​c.894+27delT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.147 in 1,136,162 control chromosomes in the GnomAD database, including 10,040 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.12 (1344 hom., cov: 29)
  • Exomes 𝑓: 0.15 (8696 hom.)
• Consequence: MRPL3 NM_007208.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.70
• Publications: 0 publications found

Genes affected

MRPL3 (HGNC:10379): (mitochondrial ribosomal protein L3) 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 that belongs to the L3P ribosomal protein family. A pseudogene corresponding to this gene is found on chromosome 13q. [provided by RefSeq, Jul 2008]

MRPL3 Gene-Disease associations (from GenCC):

• combined oxidative phosphorylation defect type 9

  Inheritance: AR Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
• mitochondrial disease

  Inheritance: AR Classification: MODERATE Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP6: Variant 3-131468063-GA-G is Benign according to our data. Variant chr3-131468063-GA-G is described in ClinVar as Benign. ClinVar VariationId is 1292149.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.193 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007208.4. 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
	MRPL3	NM_007208.4	MANE Select	c.894+27delT		intron	N/A	NP_009139.1	P09001

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MRPL3	ENST00000264995.8	TSL:1 MANE Select	c.894+27delT		intron	N/A	ENSP00000264995.2	P09001
	MRPL3	ENST00000425847.6	TSL:2	c.975+27delT		intron	N/A	ENSP00000398536.2	E7ETU7
	MRPL3	ENST00000511168.5	TSL:2	c.936+27delT		intron	N/A	ENSP00000424107.1	H0Y9G6

Frequencies

GnomAD3 genomes AF: 0.120 AC: 17410 AN: 145422 Hom.: 1342 Cov.: 29

Gnomad AFR AF: 0.0294

Gnomad AMI AF: 0.161

Gnomad AMR AF: 0.0820

Gnomad ASJ AF: 0.253

Gnomad EAS AF: 0.0652

Gnomad SAS AF: 0.203

Gnomad FIN AF: 0.167

Gnomad MID AF: 0.195

Gnomad NFE AF: 0.165

Gnomad OTH AF: 0.123

GnomAD2 exomes AF: 0.142 AC: 20961 AN: 147252 AF XY: 0.149

Gnomad AFR exome AF: 0.0253

Gnomad AMR exome AF: 0.0505

Gnomad ASJ exome AF: 0.254

Gnomad EAS exome AF: 0.0364

Gnomad FIN exome AF: 0.167

Gnomad NFE exome AF: 0.162

Gnomad OTH exome AF: 0.143

GnomAD4 exome AF: 0.151 AC: 149891 AN: 990668 Hom.: 8696 Cov.: 12 AF XY: 0.153 AC XY: 76591 AN XY: 500828

African (AFR) AF: 0.0238 AC: 473 AN: 19886

American (AMR) AF: 0.0578 AC: 1205 AN: 20852

Ashkenazi Jewish (ASJ) AF: 0.231 AC: 4129 AN: 17882

East Asian (EAS) AF: 0.0715 AC: 2246 AN: 31404

South Asian (SAS) AF: 0.184 AC: 9358 AN: 50924

European-Finnish (FIN) AF: 0.165 AC: 7563 AN: 45836

Middle Eastern (MID) AF: 0.139 AC: 582 AN: 4182

European-Non Finnish (NFE) AF: 0.156 AC: 118443 AN: 757950

Other (OTH) AF: 0.141 AC: 5892 AN: 41752

GnomAD4 genome AF: 0.120 AC: 17412 AN: 145494 Hom.: 1344 Cov.: 29 AF XY: 0.121 AC XY: 8557 AN XY: 70780

African (AFR) AF: 0.0294 AC: 1154 AN: 39290

American (AMR) AF: 0.0819 AC: 1194 AN: 14572

Ashkenazi Jewish (ASJ) AF: 0.253 AC: 864 AN: 3412

East Asian (EAS) AF: 0.0654 AC: 326 AN: 4986

South Asian (SAS) AF: 0.203 AC: 941 AN: 4628

European-Finnish (FIN) AF: 0.167 AC: 1549 AN: 9286

Middle Eastern (MID) AF: 0.205 AC: 57 AN: 278

European-Non Finnish (NFE) AF: 0.165 AC: 10931 AN: 66144

Other (OTH) AF: 0.126 AC: 253 AN: 2010

Alfa AF: 0.0419 Hom.: 48

Bravo AF: 0.102

Asia WGS AF: 0.135 AC: 466 AN: 3450

ClinVar

ClinVar submissions

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
PhyloP100		-2.7
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: rs374998359; hg19: chr3-131186907; COSMIC: COSV99395134; COSMIC: COSV99395134;