NM_007208.4:c.816+161_816+162dupGT

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

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

• Frequency: Genomes: 𝑓 0.032 (84 hom., cov: 0)
• Consequence: MRPL3 NM_007208.4 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.00
• 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-T-TAC is Benign according to our data. Variant chr3-131469533-T-TAC is described in ClinVar as Likely_benign. ClinVar VariationId is 1198044.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.0325 (4771/146964) while in subpopulation SAS AF = 0.0514 (238/4626). AF 95% confidence interval is 0.0461. There are 84 homozygotes in GnomAd4. There are 2364 alleles in the male GnomAd4 subpopulation. Median coverage is 0. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 84 AR gene

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+162dupGT		intron	N/A	NP_009139.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MRPL3	ENST00000264995.8	TSL:1 MANE Select	c.816+162_816+163insGT		intron	N/A	ENSP00000264995.2
	MRPL3	ENST00000425847.6	TSL:2	c.897+162_897+163insGT		intron	N/A	ENSP00000398536.2
	MRPL3	ENST00000511168.5	TSL:2	c.858+162_858+163insGT		intron	N/A	ENSP00000424107.1

Frequencies

GnomAD3 genomes AF: 0.0325 AC: 4768 AN: 146852 Hom.: 83 Cov.: 0

Gnomad AFR AF: 0.0183

Gnomad AMI AF: 0.0831

Gnomad AMR AF: 0.0260

Gnomad ASJ AF: 0.0417

Gnomad EAS AF: 0.0390

Gnomad SAS AF: 0.0516

Gnomad FIN AF: 0.0367

Gnomad MID AF: 0.0400

Gnomad NFE AF: 0.0389

Gnomad OTH AF: 0.0303

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

GnomAD4 genome AF: 0.0325 AC: 4771 AN: 146964 Hom.: 84 Cov.: 0 AF XY: 0.0330 AC XY: 2364 AN XY: 71678

African (AFR) AF: 0.0184 AC: 736 AN: 40102

American (AMR) AF: 0.0260 AC: 382 AN: 14710

Ashkenazi Jewish (ASJ) AF: 0.0417 AC: 142 AN: 3402

East Asian (EAS) AF: 0.0385 AC: 184 AN: 4782

South Asian (SAS) AF: 0.0514 AC: 238 AN: 4626

European-Finnish (FIN) AF: 0.0367 AC: 365 AN: 9932

Middle Eastern (MID) AF: 0.0464 AC: 13 AN: 280

European-Non Finnish (NFE) AF: 0.0389 AC: 2576 AN: 66242

Other (OTH) AF: 0.0305 AC: 61 AN: 1998

Alfa AF: 0.0349 Hom.: 533

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
PhyloP100		0.0
Mutation Taster		=100/0	polymorphism

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs3830301; hg19: chr3-131188377;