3-131469533-TACACACACACACAC-TACACACACACAC

Variant names:

• chr3-131469533-TAC-T
• rs3830301
• NM_007208.4:c.816+161_816+162delGT

Variant summary

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

The NM_007208.4(MRPL3):​c.816+161_816+162delGT variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.55 (21722 hom., cov: 0)
• Consequence: MRPL3 NM_007208.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.888
• Publications: 1 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: Ambry Genetics, Labcorp Genetics (formerly Invitae)
• mitochondrial disease

  Inheritance: AR Classification: MODERATE Submitted by: ClinGen

ACMG classification

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

• BP6: Variant 3-131469533-TAC-T is Benign according to our data. Variant chr3-131469533-TAC-T is described in ClinVar as Benign. ClinVar VariationId is 1259936.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.621 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.816+161_816+162delGT		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.816+161_816+162delGT		intron	N/A	ENSP00000264995.2	P09001
	MRPL3	ENST00000425847.6	TSL:2	c.897+161_897+162delGT		intron	N/A	ENSP00000398536.2	E7ETU7
	MRPL3	ENST00000511168.5	TSL:2	c.858+161_858+162delGT		intron	N/A	ENSP00000424107.1	H0Y9G6

Frequencies

GnomAD3 genomes AF: 0.549 AC: 80316 AN: 146404 Hom.: 21713 Cov.: 0

Gnomad AFR AF: 0.628

Gnomad AMI AF: 0.531

Gnomad AMR AF: 0.553

Gnomad ASJ AF: 0.496

Gnomad EAS AF: 0.342

Gnomad SAS AF: 0.417

Gnomad FIN AF: 0.507

Gnomad MID AF: 0.580

Gnomad NFE AF: 0.532

Gnomad OTH AF: 0.557

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.549 AC: 80368 AN: 146514 Hom.: 21722 Cov.: 0 AF XY: 0.543 AC XY: 38779 AN XY: 71420

African (AFR) AF: 0.628 AC: 25113 AN: 40006

American (AMR) AF: 0.553 AC: 8119 AN: 14678

Ashkenazi Jewish (ASJ) AF: 0.496 AC: 1682 AN: 3392

East Asian (EAS) AF: 0.342 AC: 1629 AN: 4766

South Asian (SAS) AF: 0.418 AC: 1930 AN: 4614

European-Finnish (FIN) AF: 0.507 AC: 4969 AN: 9806

Middle Eastern (MID) AF: 0.568 AC: 159 AN: 280

European-Non Finnish (NFE) AF: 0.532 AC: 35190 AN: 66094

Other (OTH) AF: 0.555 AC: 1103 AN: 1986

Alfa AF: 0.341 Hom.: 533

Bravo AF: 0.563

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		0.89
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs3830301;

hg19: chr3-131188377;

COSMIC: COSV53913758;

COSMIC: COSV53913758;